[TRC] Summer 2023 Research Journal

A systematic review of the application of CAR- T Cells within CRISPR/CAS-9 Technology: An insight into its abilities and limitations regarding various diseases

Helena Kaaua, Helen Ejigu, Zena Brantuo, Kayla Shaw, and Arya Soppanawar Mentor: Giovanna Napoleone, Columbia University

Abstract Materials and Methods

Chimericantigenreceptor(CAR)T-ce ltherapyhasbeensuccessfulin treatingleukemias,lymphomas,andmyelomas WithinCART-celltherapy, theCARcel s,whicharereceptorT-cellsthathavebeenmanufacturedina lab,containanewreceptorsothattheycanattachtocancercellswhile killingthem Witha50-80%averagesuccessrateinuti izingCART-cel therapy,thismechanismiscurrentlybeingusedforapp icationsassociated withCRISPRtechno ogy DespitethetriumphsofCART-cel therapy,there arestilldrawbackssuchaslethaltoxicities,refusaltoacceptinB-cel ma ignancies aswellasitsvar edefficiencyagainstsolidtumors Withthe riseofCRISPRgeneed ting,itispossibletomitigatesomeofthese drawbacksthoughanintersect onbetweenthetwomethods CRISPR (Clusteredregularlyinterspacedshortpalindromicrepeats)isageneediting toolthatcantransformDNAentirelythroughadding,omittingandaltering thegeneticmaterialat ocationsthroughouttheorgan sm WithCRISPR technology,variousdiseaseshavebeentreated,includingbutnotl mitedto: breastcancer,coloncancer,lungcancer sick ecelldisease,andbeta thalassemia NewresearchhighlightsadditionalCRISPR-Cassystem variet es,includingm niCasorCRISPRIwhichcanbesupplementedfor geneediting ThisreviewevaluatestheabilitiesandrestraintsofCRISPRCas9editingwiththeappl cationofCAR-Tcellsinclinicaltrials

Introduction

Genesareafoundationalpartofthehumanbody,asthey areportionsofDeoxyriboseNucleicAcid(DNA) By alteringspecificsequenceswithinDNA,geneediting technologyhasthepotentialtocuregeneticdisordersand cancers Partofthisnewtechnologyincludesthegeneediting technologyofCRISPR-Cas9 TheCRISPRtechnologyis abletorewritegeneticmaterialthroughutilizingRNAasa guideforCas-9,anenzymetolockontoaspecificspoton theDNA,thereforeunzippingitandsplittingthegenetic materialapartcausingtheorganismtoself-heal While CRISPRistakingcontrolofgenetherapy,thereisalso anotheralternativenamedCART-celltherapy CART-cell therapycontainstheCARcells,whicharereceptorT-cells thathavebeenmanufacturedinalab,containinganew receptorsothattheycanattachtocancercellswhilekilling them Asdiseasescontinuetowipeoutpopulations,scientists utilizebothCART-cellsandCRISPR,aimingtodiscover remedies Assuch,thereisaclearneedandabilitytoconjoin thetwoinformingCRISPRtherapythathasanapplication withCAR-Tcells.

Discussion

This systematic rev ew follows a comprehensive l st of c inica trials n regards to CAR T-cell therapy treatments for future appl cations w th the CRISPR system The clinical trials were col ected from PubMed, C inica Tr als gov and the Nat onal Center for B otechnology The fo low ng searches were performed: “CAR T-ce l therapy ”

“CRISPR treatment with eukemia,” and “CRISPR-Cas9 treatment in S ckle Cell Disease, Alzheimer’s, Beta Thalassemia and Lymphoma ” On y trials conducted within the past 5 years were se ected The fol owing nformat on was co lected across studies: d sease type, number of people tested, and number of people cured The data collected from the tr a s were supplemented with publ shed sc ence journals and art cles that explained new CRISPR and CAR T-cel therapy techniques and the r appl cations to var ous diseases Any l mitations to th s study may nclude variable experimental factors conducted in each clinica tria not controlled through the ana ys s of this l terature review, for the purpose of ind vidua laboratory studies outside the scope of this rev ew Tria s that d d not meet our analys s standard of five years and off a cl n cals tria s database or webs te or were unava lab e to open rev ew were excluded from the data col ect on process

CRISPR Technology

Asnewadvancementsofgenetherapybegintosurface,CRISPR-Cas9hasaready madestrdes ntheresearchandapplicatonofgenomeeditingtechnoogy,despiteits short ifespan Thesystemnotonlyrecognzesgeneticmutatonswithinthehuman genome,butdrectlyatersDNAsequencesandmodfiesexstnggenetcmaterial wthfarmoreprecisionandaccuracyincomparisonto tscounterparts CRISPRCas9iscomposedoftwomaincomponents:1)theCas9protein inkedtothetarget cell,and2)theguideRNAwhchdirectstheproteintomodifythepreciselocationof themutation AstheRNAfirstrecognizesthetargetedsequenceandismetwiththe matchngDNAsequence,thegudeRNAiscoupledwiththeCas9protein atwhch ponttheRNAsequenceis dentifedtoeitherbereplacedoraddedontoanexisting DNAstrand InFgure1 thesystemdemonstrateseitheramodfication(pairedwith thehomologouscombination)orcompetereplacement(non-homologous combinaton)ofaDNAsequenceusngtheCRISPR-Cas9system

CAR-T Therapy

Results

W th the data col ection stemm ng from multiple clin cal trials, each with ts own un queness and specificity it is imperative to draw correlat on ana ys s and formulate inductive conc us ons regarding CRISPR-CAS9 and CAR-T therapy Meanwhi e, as CAR-T cel therapy tria s were on y avai able for two d seases, he l mited data cannot produce a valid conclusion as to whether CAR-T ce ls can be mplemented with CRISPR Specif cal y with Leukemia in regard o CRISPR therapy, the cl n ca tria at GOSH y e ded a ower recovery rate than the tria with CAR-T It should be noted, however the tr al w th CRISPR-ed ted T cel s had on y 6 peop e and a 25% recovery rate wh le the CAR-T tr al had 75 peop e and a 73% Whi e the CRISPR recovery ra e n Leukem a was ow, an ongoing Lymphoma CRISPR tria with CAR-T ce ls has a 69% recovery rate thus providing a platform for a logical conclus on that CRISPR and CAR-T comb ned could y e d a higher recovery rate than any tria that uses only one of the methods

CART-celsaremodfiedt-cel mmunecellsusedtotackecertaincancersCARTcelsuseachimercantigenreceptor(CAR)whchgivesthemtheabiltytomore effectvelyseekoutanddestroycancerouscelsthanahost’snatvet-celsThe chimercantgenreceptor,seeninFigure2,isanartficalproteinandsourcesits cancerfightingpropertiesfromitsunquecombinationofstructuresspecifctoa targeteddiseaseAsseeninFgure2,the“head”orextraceluarportionofthe chimericantigenreceptorconsstsofaprotenknownasscFvScFvissourcedfroma specificantibody’sheavyandlightchainsandcombinedwithapeptdeinkerrangng anywherefrom10-25aminoacidsScFvcontainsthesameantgen-bndngspecificity oftheantbodyusedtomakeit,whchcontrbutestothespecfictyoftheCART-cell beingcreatedtotargetadiseaseOntheotherhand,the“tai”intracelularportonof thechmericantigenreceptorconsistsofaCD3zetadomanThisportonofthe chimercantgenreceptorssourcedfromtheCD3compexwhchsresponsiblefor activatingat-cellduringanimmuneresponsenthepresenceofaspecficantigento aidthet-celreceptors(TCR)TheCD3zetadomanisresponsibleforconnectingthe ntracellular,sgnatransductionpathwaysresponsiblefortrggeringaT-celmmune responsetotheextracelluarantgenrecognitionandbindngThechimercantigen receptorpossessesbothscFvandCD3zetaprotens,hencetheterm“chimerc”The chmericantigenreceptorcouplestheantigenspecificityofscFvandtheablityof CD3zetatotriggeranimmuneresponseofagivenT-cel

Beta Thalassemia and Sickle Cell Disease

Applications of CAR-T related methods to tackle varied diseases S ck e Ce D ease has een unpr cedent d u ces w th s app ca on regard ng CRISPR h rapy Mo t common y known a s ck e ce d eas , a b ood d sorde that genet c au ng ed b ood e l o h nk nto a s ck e hape h se ce d e p ema ure y eav ng hea thy b ood ce s by h m e ves B ta ha a sem a i ano her m ar b ood d sorder hat edu es he p oduc on o hemog ob n an p o e n car y ng on n red b ood ce s hat d s r bute oxygen o ce s amongs h body The con ra t ng a tor be ween h d f er n at on o h two d sea es s hat SCD s genera ed by a pec f muta on n h HBB gen wh e BT can ar se a a re u of seve a mu at ons w th n the ame g n Trea ng SCD a ongs de CRISPR u i es an ex v vo me hod wher HSCs s em ce s ar om t ed f om h body al e ed, hen n er ed back n o he body As doing such w s mu at the product on o new e y hrocy es hi me han sm a so genera es a ack on BCL11A wh ch nh b s he p oduc ion of HBG1 thus preven ng he prot in rom xpand ng and HBG1 an g ow The p c f c ype of HSCS ha ar pa sed on CD34+ e s the e ce a e ab e to econ t uct ry h o yte n o the hema opo et c ys em Fol ow ng th s damaged or d sea e-caus ng e s ar om t ed h ough chemo herapy and CRISPR d ed ce s a e e n e ted nto a pat en s body Pa ent w th BT and SCD have shown un ema kab e outcomes n r a s spe i ca y the CTX001 r a Resu s rom a r a conta n ng pat en s rea ed onc w th CTX10001 d p ay he n ended re u s w h mos t s subj ct di p ay ng h ghe eve s o h mog ob n n he r b ood W th n CTX001, he s em ce s a e tw ak d o gen ra e HbF a orm o oxyg n w h h mog ob n tha s pre ent a b th h n s egenera ed to h adu orm of hemog ob n Pha e 1 of he t a inc uded 75 pa ent (31 w h S ck e Ce Di eas and 44 w th Be a Tha ass m a o wh ch hes pa ent had a o ow-up rang ng f om 1 2 to 37 2 month Ou o he BT pat en s 26 exh b ed b ta-ze o genotype howeve 42 o h BT pat en s we e rans u on re and the o h r wo pa ent who we e no rans u on re had an 89% and 75% edu t on in he r rans u on vo ume L kew e al 31 pat n s w h SCD we e f ee o VOC a cr i occurr ng when comprom ed red blood ce s obs ruc b ood ow to wher the ssue b come oxygen dep ved The r HbF l ve s had sen by about 40% and cont nued to rema n the ame or mon h Among the BT pa ent on y 2 had ymptoms uch a ARDS and HLN a we as an unknown pneumon a symptom tha ar sed The tudy ha now progr ss d o Phase 3 now a low ng for ag s 2 th ough 11 year o par c pat and w t an ate o chi d en 2 and under a e n regard to CAR-T C l Th rapy th s appl a on has no be n a r bu ed o i her o the e di eas s As uch CAR-T ce the apy mus b conduct d on the e wo d s ase be ore orm ng a va d conc us on on whe h r CAR-T ce s w h CR SPR t chno ogy ou d b app cable to SCD and BT

References

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ErnMOeeA,BesirogluBCaro-ValnzueaJAbdEAzzMMonse BochmannPEscourLJSkoezNGoldkuheMChmrantgen rceporCAR)T-ehrapyopoplwhrlapedoreacoryduse argB-ceymphomaCochaneDatabaseSysRev.2021Sp 1399)CD013365.do10.1002/14651858.CD013365.pub2.PMID34515338; PMCIDPMC8436585

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oh s n LA S ho J O ku T Ko ak A Pa PR McGe an E Na AK D n h v T Th k a P L ew A Bo s an AC Co d AP Ch n T F e JA K o s CC P s y AD J En e s B S n h R Ez T damak n N R mo e MH L N Z ou L P e a G e ko a T Oka a H un CH B o don JL M u MV R ona d v opmen and c a a e a o o h ma z d n -EGFR v r n c m r c n g n e p o T e o o a om S T an M d 20 5 F b 1 7 75 7 r 2 do 1 11 6 an m d a 49 3 M D 2 69 0 1 PMC D PMC 4 71 6 K A D a B J Ca a ne C M e CRI PR c n e b o o y nd he a y Na Re Can r 2 20 2 59–2 9 K e C B oo e d c k o ne r t x y om CAR T-c h ap Hea hc e Eu op 02 3 K e m n RM e Th uk m n Ne o Te book o P d a 2 s d E s v 02 Mag L Ca a eo G Da AE Mo had am AS nd F on S CAR T C -B s d mmuno e a y o h T e m n o G o a om F on Neu o 02 5 6 2 64 do 10 33 9 n n 20 1 6 06 Mau e L La s h TW Bu hn r J R e S Boy M B e co r H Bad P Ve n MR S e n k HE My r GD Qa ed M D Mo r o e B H am s H c K Da s KL Ma n PL N m c k ER Yan GA P e C Ba u h A Bo e N M c na d F Ba du z A Kr e e un CH Le ne BL Wood P Ta an T Le ng M M e KT Z an Y Se K L bwoh D P ph r MA Gr pp A T g n c u e n Ch r n nd Yo ng Adu s w h B-C Lymph b a Le kem a N En Med 20 8 F b

Figure 3: CTX001 Therapy displayed in regards to SCD and BT

A systematic review of the application of CAR- T Cells within CRISPR/CAS-9

Technology: An insight into its abilities and limitations regarding various diseases

Helena Kaaua, Helen Ejigu, Zena Brantuo, Kayla Shaw, and Arya Soppanawar Mentor: Giovanna Napoleone, Columbia University

Discussion

Cancers

Cancer s a d sease that originates rom mutat ons in genet c codes of DNA lead ng to abnorma cel divis on and grow h Protooncogenes, tumor suppressor genes, and DNA repa r genes become most af ected by genetic changes that contr bute o cancer, due to the r important roles n the cyc e cycle Both protooncogenes and tumor suppressor genes are responsib e or contro ing cel growth and when an al eration occurs to these genes they might div de n an uncon rol ab e manner When protooncogenes are overact va ed they become oncogenes genes (cancer caus ng genes) When umor suppressor genes become inac ivated, they a low he growth of a tumor, and are a so cancer-caus ng DNA repa r genes are nvo ved in f x ng damaged DNA thus when a mutation occurs w thin these genes uncon rol ab e dup ications and de et ons of chromosomes can occur wh ch may develop nto cancerous ce ls Uncontro ab e ce l growth can ult mately ead to the ormation o cancerous umors that spread hroughou he body, a process cal ed metas asis In order to prevent cancerous gene mutations rom occurr ng sc en ists over the years have been search ng to f nd methods of contro l ng tumor growth and he genet c errors that can lead to cancer Based on recent stud es both CRISPR Cas-9 and CAR T-cel herapies can potential y be used to targe cancer caus ng genes and tumors Sc en ists are using CRISPR to genetica y a ter mmune system ce ls known as T-cel s rom hea thy donors to e fec ive y at ack cancers hrough CAR-Tce l mmunotherapy Using his approach T- cel s are taken from a pat ent’s b ood and become genet cal y modi ied by add ng a gene w th n the CRISPR ed t ng comp ex o a ch mer c an igen receptor (CAR)ch mer c an igen receptor (CAR) By re-eng neer ng the -ce l receptor prote ns, the CAR can recognize and bind to spec f c an igens presen on the surface o cancer cel s This a lows the T- cel s o ef ect vely attack a spec f c cancer ce , targe ant gen Cancer ce ls can evade the mmune system by b ock ng mmune checkpoin recep ors and overs imulat ng per phera tolerance Cancer cel s can also m mic mmune checkpoin recep ors, lead ng to T-ce ls not detect ng them as harm ul For example, one of the ma n immune receptor proteins ca led PD-1 nteracts wi h another receptor cal ed PD-L1 to s gna when a hea thy cel s present and its expression on cancerous tumor ce ls crea es an mmunosuppressive environment for the umor Th s effect is detrimenta owards CAR T- ce ls as t lowers its act vation and response rates CRISPR assists in the construction of CAR T-cel s able to de ect these cancerous cel s by ensur ng the correc “off” s gnals are p aced on the receptor through a checkpoin nhibit on Act va ed or “on” CAR T- cel s mu t ply and s gnal through cytokines (s gna ing proteins) Both act vated CAR- T- cel s and cytok nes then causes s gn ficant in lammat on of the cancer cel , eading o apoptos s The revamped CAR T- cel s are nfused back nto the pat en o mu tip y and streng hen the immune system Somet mes CAR-T- cel s are turned “of ” and stop ki ing cancer cel s a phenomenon known as T-ce l exhaus ion Sc entis s be ieve T-cel exhaust on may be l nked to transcrip ion factors proteins that regula e a ce l turn ng on and of via gene activat on or nact vation dur ng transla ion However CRISPR Cas-9 has the capab l ty to create ed ts hat can m n m ze T-cel exhaust on and increase he r long erm prol ferat on, wh le l mit ng CAR-T-ce l tox city Most trials done on cancer us ng CRISPR and CAR T-ce l technology today are o rea ymphoma and eukemia There are several d fferent c in cal trials involving cancer hat are current y ongo ng two of wh ch th s rev ew wi l consider for analys s that w l take both CRISPR and CAR T-ce l therapy techno og es nto considera ion

Lymphoma

Lymphomasacancerofthelymphaicsysemandisanoverarchngermtodescrbeacuseroblooddiseasesthatpuncturesbonemarrowandproducesan enargemenoflymphnodesTherearetwomaintypesoflymphomas:HodgkinandNonHodgkinsHodgknymphomahasaspecfcypeofymphocyte Reed-Sternberg)assocaedwihthediseaseandNonHodgknsymphomadoesnohavethsceypepresentManyrialsfocusedonreatngymphoma havebeeneffectvethroughtheteatmentofregularCAR-TCeltherapyBecauseoftseffectvenessrecentresearchindicateshaheserialsmaybe mprovedthoughhempementatonofnewCRISPRtechnoogyInaphaseIIIrialcontaningpaienswihB-celymphomawhorecevedax-celCART celtherapy,180patentshadax-celtherapyand179patentshadstandardcartreamen,wthanntendedoutcomeo-even-freesurvvalAfer45years researchersoundhahenumberodeathshadrisento45%inheax-celtherapygroupand53%nthestandardcaregroupInaddiion,a147month Progresson-reesurvivaate(PFS)wasoundntheaxi-celcohortand37monthPFSwasfoundinhesandardcaregroupAPhase1cinicatrautlzing CRISPRjoinlywihCART-cesemergedn2023toreatnon-HodgkinymphomaThetraadmniseredT-celswthanncreasedeffciencybyaddinga molecuenamed1XXwthntheCARandinectngtintheDNAThemesothein1XXsengneeredoproongCAR-Tcelswthoutdeveopngexhausion wthnthecesTherialwasconductedattheMemoraSoanKetterngCancerCenter(MSK)andsprogressngontoPhase2rialwihareponserateof 69%-aratewhichremanednactatera155dayfolowupTheCRISPRmodewibeessentaincreaingnewCARcesabeoargecancesatmore specfcocatonsbytargetedDNAstrandsequencesreaingtoymphoma,oranyboodcancerFgure3dspayshecyceofCRISPRnregadsobood cancerhighlghtngtheproductonofTRACPDCD1andTRBCociwhicharethenbndedwthaentvralvectorandthenpubackintotheboodsream TheseindingsindicaehaheresapotenialforappynghionttherapytootherdiseaseHoweverischalengingtoproveheeficacyasthetraof theCAR-TCelsandCRISPRhasnotyeinshedandwlnotforanotheryear

Figure 4: Displays T-cells being detached from a patient with b ood cancer CRISPR-Cas9 proteins are filled with 3 sgRNAs yielding a gene edit to create TRAC, PDCD1, TRBC loci A entivira vector is applied to the cells intended for gene expression for specific antigens F na ly, the CRISPR manufactured T-cells are re njected back into the patient

References

Leukemia

Leukem a descr bes a broad spect um o cance s a get ng h b ood sp cia y ones ha invo ve blood ce format on d ve opment and funct on Leukem a harac er zed by mu a ons n both the ce yc e and he tem ce yc e which are c as i ed as ymphocy c or myelogenous eukemia No ma y mmature s em c l known a lymphoid o mye o d form and proce s as wh e b ood ce s The e ce s ar yp ca y ex rac ed rom he pongy i sue composed n ide of bone s ructure and a e cr t ca to he generat on o new ce s Leukem a occurs when a mu a on o cu s wi hin he no ma ce l cyc e

Acu e Leukemia nvo ves mma ure s em ce s ha have no ful y developed ye but prol era e beyond con rol In compar son chron c Leukem a nvo ves ma ure or par a ly ma u e ce s that have become mu ated p even ng them rom ca rying ou he r n ended func on Once a ce muta es i rap d y mul p e and overc owds hea hy b ood ce s rom occupy ng he pace avai abl w h n the bone marrow I e t untr a ed, h se ce s may spread throughout h body and the di ease can p ead o cr a e tumor and a ect ssues and organ rom unc ioning p oper y I cr t ca for pat ent o rece ve he r ght care and a tent on o rad ca e these cancerou ce l be ore fur h r p ogr ss on of he d sease occurs Current y sc ent s s are a ses ing the e fec v ne s o CAR-T-ce therapy and CR SPR-Cas9 for a comple e rem ss on of eukem a pat ent n seve al c ni a r al Pr or to CR SPR-Cas9 techno ogy CAR-T-ce he apy ha produced s gn can resu t n the rem ss on a es of hou ands o pa en s bat ing al our ypes o eukem a Tr a EL ANA Novart ) nvo ved ch ldren and young adu s w th B-ce Acu e Lymphocyt c Leukem a (B-ALL) who prev ous y re apsed or d d no respond to o h r forms of he ap es Phase 1-2a nvo v d he usage o an -CD19 ch mer c ant gen eceptor CAR) T-ce therapy v a t sagen ec euce re u ing n high comple e rem ss on a es among t part c pan s Th r a wa la er ound o have produced ser ou toxi , bu ma nly r v rs ble adverse e ect among ch d re ated and young adu t n Phas 2 of he c n ca r a , he tudy expanded o a g oba study where a s ng e cohor was t eated to te t sagen ec euce n ped at c pa i n s and young adu s A the end of he r a , c en s s hoped o ach ev ul comp ete em s ion o a pa i n s w th n 3 mon hs o t med- n erva n u ions W h n the s udy, 75 pa en s ece v d a s ng e do e o t sagen ec euc l an ant -CD19 CAR T-ce he apy n he o m of nfus ons Op ma resu t were def ned a h gh em ss on ate comp ete r m ss on or comp ete em s on w h ncomp e e hemato og s recovery w h n 3 mon h o he f r t do age At he end o the s udy, he ev n - ree overa surv va ra e was es mated at 73% of a pa i n s New corre t ve measure in CAR T-ce herapy a gned w h CRISPR techno ogy o ncrease ota recovery rat s amongs pa en s In a c n ca r al conducted by r searcher a Gr a Ormond Str et Hosp ta for Ch ldren (GOSH) and UCL Great Ormond S ree In t u e o Ch d Hea th (UCL GOS CH) r searchers used CR SPR-Cas9 techno ogy o genet ca y d donor T-ce s u ed o CAR-T-ce therapy W th n h r a T-ce s wer mod f ed v a h CRISPR-Cas9 echno ogy to ns rt a genet c code wh ch he p d re t he T-ce in revea ng he h me c an igen recep o used o detec a targe marker and r ct y umo ous b-c l The r a con s ed of 6 pa en s rang ng f om 14 months o11 years of age w th B-ALL who re apsed o we e unrespons ve o prev ous o ms of herapy Of he 6 pa en s 4 wen n o em s ion or 28 days af er r al analy i Cur en y 2 pa en s ema n n rem s on for 9 mon hs and 18 mon hs A though h se resu t may not nc ude h gh rem s on rat s amongs al part c pan s the 2 rema n ng pa en s n rem s on revea recovery resu t that ca for u u e c in cal r a s nvo v ng both CAR-T-ce the apy and CRISPR echno ogy Because o the m ta ons and po s b e s de ef ec s presen in CAR-T therapy CRISPR echno ogy can u i ze T-donor c l and e ect ve y revo ut on ze h uture of mmunotherapy a toge he

Alzheimer's Disease

Alzheimer’s d sease is the most common neurodegenerat ve d sorder It is defined by the abnormal accumu ation of tau, a prote n essen ia in maintain ng the structure and stab l ty of the cell s nternal transport system in the neurons, and amy oid beta Aβ a protein fragment that s a key component of amy o d plaques The CRISPR-Cas9 system was developed to improve sequence-spec fic gene edi ing n ce l ines and animals Including cancers and other blood disorders he technology has served as a too or treat ng human genet c d seases ncluding Alzhe mer’s In prev ous years, animal models of Alzheimer’s have been generated by overexpressing mutated genes from humans nvo ved in the product on of the tau and Aβ prote ns Tes ing the prote n s funct ons within mouse mode s, researchers at he Un versity of Ca ifornia San D ego ound that CRISPR gene edit ng treatments have led to the reduc ion of beta-amy oid p aques and assoc ated markers of bra n nflammation These stud es have also found an increase n neuroprotect ve APP (amy oid precursor prote n) products and a correct on of behavioral and nervous system funct on deficits These an mal mode s have been he p u , but have been unable to deve op overt neurodegeneration symp oms found in humans As a resu t, CRISPR-Cas9 techno ogy s now be ng used to create A zheimer s disease models that show a more accurate d sease phenotype for the purpose of finding new avenues of treatment and therapy To reduce Aβ product on Cas9 act vators and nh bitors have been emp oyed A catalyt ca ly inactive Cas9 (dCas9) has been comb ned w th gene act vators and inhib tors, wh ch are dr ven o the target gene through the guidance of RNA However, instead of prompt ng a doub e-strand break of DNA, a general transcriptiona activator or inhibitor is carr ed w th the dCas9 system to increase or decrease the express on of the target gene Several research groups have generated Cas9 activator nano comp exes and non-v ra del very systems wi h po entia therapeutic appl cat ons This approach has been successfu n vivo to decrease the express on of BACE-1 The result was the reduct on of Aβ production and the concom tant amel orat on of AD-l ke patho ogy The potentia appl cat ons of CRISPR-Cas9 have been successful y tested n a variety of animal models, and emerging c inical tria s are being planned to test it on humans CAR-T cells have also a tracted the attent on of sc ent sts over the past 10 years CAR-T ce ls have made str des n treating neurolog ca cancers such as Gl ob as oma and Neurob astoma, due to the r abi ity to cross the b ood-brain barrier and use various targets However the use of CAR-T ce l therapy in treating neuro ogical d sorders/diseases, such as Mul iple Sc erosis s sti l be ng investigated as a potent al treatment option In Mul iple Sc erosis, CAR-T ce l therapy has been wel to erated and rare y assoc ated with rreversib e CNS adverse events Thus ant -CD19 CAR-T cel s represent a h ghly po ent tool for dep et ng CD19+ B cells in the per phery and the CNS mak ng them a v ab e treatment strategy or testing in patients with MS as we l as in o her neurodegenerative d seases

Limitations

Whi e CRISPR Cas9 s a revo ut onary technology ha has l m tless app ications when used to mprove CAR T-ce l the apy, t has notable l m ta ions

CRISPR Cas-9 s not 100% accurate and re iab e and as such o f- arget edi s unwanted or unexpected changes to the gene) can occur This may re ul n undes red mutat ons which can affect the viab l ty of a patien ’s DNA to a arger extent

CAR T-cel therapy has been nked to neuro ox c ty Two side ef ects are common as a re ul of the trea ment cytok ne re ease syndrome (CRS) and mmune e fector ce l-assoc a ed neurotoxic ty syndrome (ICANS)

CRISPR materia s d ff cul to del ver to mature ce s n arge quan i ies emain ng a prob em or many c nical app ica ions

The long-term consequences o CRISPR gene ic mod f cat ons are not wel unders ood and he ab l ty o edi a human germl ne ra ses ethical concerns

CRISPR-Cas9 echnology yie ds eth ca deba es abou ts regulatory afety measures possible gene mutat ons that cou d transfer reproduc ively or affect future generat ons and genet c diversi y as we l as a poss ble exp o tat on of pat ents who choose o be e t sub ec s

Conclusion

The mp cat ons of CRISPR and i s po ent al ef ec s when be ng used w th CAR T-ce herapy s h gh y var ed amongst di feren di ease condi ons Be ng natura y re a ed as wel a he fact that CAR-T ce l can be a product o CRISPR techno ogy refers o the s m lar t es in the condi ons ha they exce at t eat ng Cond t ons w th genet c pred spos t ons and prote n w th genet c a get arge y are be ter w h pat ent recovery outcome , and poss b e mp emen a ion of CRISPR as oppo ed to CAR T-ce l herapies Such condi ions encompass bu are not im ted o Be a Thalassem a and Sick e Ce Anem a as wel as severa neu odegenerat ve d seases uch as Alze mher s However when t comes o treat ng b ood cancer and ce cycle d seases wh ch more arge y nvo ve he immune sys em, CAR T-ce l herapy s mos e fect ve A though thi s known in curren re earch the mp ementat on of CRISPR w th n CAR T-ce l therapies may p ove o be even more e fect ve or the e cancer d seases as opposed o fo mer vers ons of the herapy Whi e the targe -spec f c natu e of CAR T-cel s n ident fy ng ce l hat a e diseased poses many advan ages over CRISPR the apies for leukem a and ymphoma, a CAR’ unc ion can be enhanced hrough he use o CRISPR Ul imate y, both CRISPR and Car T-cel s techno ogies demons ra e how varied and adap able mode n day t eatments are or d f erent cond t ons Wh le growing at a rap d pace, he fu ure o hese two intersect ons appea s prom s ng for biomed ca eng neers The brevi y o biotechno ogy tha peop e have access o oday a outc asses any h ng hat those in he past decade cou d have conceived o As such he human nnovat ons today proceed o pu h the boundar es o what can be ach evab e

2020 6 p S e anoudak s D, Ka hur a-Prakash N Sun AW Abe M, Dro en CE Ashbaugh C, Zhang S, Hu G, Tabatabaei YA Zek ser Y Lopez LP Pan uck A, Drakak A The Po en ial Revolution of Cancer Trea ment w th CRISPR Techno ogy Cancers Basel) 2023 Mar 17 15(6) 1813 do : 10 3390 cancers15061813 PMID: 36980699; PMCID PMC10046289

Tavakol K Pour-Aboughadareh A, Kianersi F, Pocza P, E minan A, Shoosh ar L Appl ca ions of CRISPR-Ca 9 as an Advanced Genome Ed t ng System n Li e Sc ences B oTech (Base ) 2021 Jul 6;10(3) 14 do 10 3390/bio ech10030014 PMID 35822768 PMCID: PMC9245484

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Wes in JR O uwole OO Kersten MJ, M klos DB, Pera es MA, Ghobad A Rapoport AP Sureda A, Jacobson CA Farooq U, van Meer en T U rickson M E sawy M Lesl e LA Chagant S, D ckinson M Dorr tie K Reagan PM McGu rk J Song KW R ede PA Minnema MC Yang Y Vardhanabhu i S F osto S Cheng P Shahan SA, Schupp M, To C, Locke FL; ZUMA-7 Invest gators K te Members Surviva wi h Ax cabtagene C loleucel n Large B-Cel Lymphoma N Eng J Med 2023 Ju 13 389 2) 148-157 doi 10 1056 NEJMoa2301665 Epub 2023 Jun 5 PMID 37272527

Zarghamian P, Klermund J and Ca homen T (2023) C nical genome edi ing to treat sick e cel disease A br ef update Fron Med 9:1065377 do 10 3389/fmed 2022 1065377

Acknowledgments

Theauthorsofthispapergratefullyacknowledgementor GiovannaNapoleoneforhertimeandeffortin developingthisresearchproject.Herknowledgeand researchguidancewasextremelyhelpfulinaidingthe authorstosuccess Theauthorsofthispaperwouldlike toalsothankTheResearchCatalystFellowshipProgram forgivingthemtheresourcesandfoundationalstructure toconductresearchanddeveloptheirideasina welcomingenvironment

Deepanalysisonwhyatrialseptaldefects occurininfants

Abstract Materials and Methods

Aholeintheatrialseptum,whichdividesthe twoupperchambersoftheheart,isthe hallmarkofanatrialseptaldefect(ASD),a congenitalheartcondition.Infantsareaffected bythisillness,whichifneglected,cancausea numberofdifficulties.Forearlydetection, prevention,andefficientcareofASD,itis essentialtocomprehendtheunderlyingcauses ofthedisorder.Byevaluatinganumberof variables,includinggeneticpredisposition, environmentalimpacts,andembryological development,thisstudyattemptstoprovidea deeperinsightofwhyASDoccursinchildren.

Introduction

Atrialseptumdefect(ASD)isacongenital heartdefectwhereaholeintheheart's septumdividestheleftandrightatrium. Thiscausesoxygen-richbloodtoleakinto oxygen-poorblood,reducingoxygendelivery toinfants.Thisraisesbloodpressureand heartrate,causingthehearttopump harder.Ifnotdiagnosedearly,ASDcan damageorgansandshortenlifespans.Most childrenwithanASDdonotshow symptoms,butseverecasesmaycauselongtermdamagetolungs'bloodvessels.

Infancy-onsetASDisinfluencedbygenetic factors,withgenevariantsandchromosomal abnormalitieslinkedtoincreasedrisk Small holeopeningsdonotcausesymptoms,but severeASDscancauselong-termdamageto lungs'bloodvessels.Earlydiagnosisand testingarecrucialforearlydetectionand treatment.

DiagnosingAtrialSeptalDefectininfants involvesdetectingaheartmurmurand orderinganechocardiogramtodetermine potentialleakage.Treatmentdependsonthe severityandlocationofthelesion,with surgicalornon-surgicalprocedures commonlyusedtotreatASDinbabies: Surgicalrepairisoftenrecommendedfor newbornswithlargerASDsorsymptoms linkedtotheabnormality.Atrialseptal defectclosureisthemostpopulartreatment, sealingtheatrialseptumholewithapatch orsuturesafterachestincision.Catheterbasedinterventionshavereplacedopen heartsurgeryinsomecases,enteringthe heartviabloodarteries.TranscatheterASD Closureinvolvesinsertingacatheterintoa bloodartery,sealingtheatrialseptumhole withadevice.Balloonatrialseptostomyisa temporarytreatmentforsevereASDs, temporarilyimprovingbloodflowand alleviatingdiscomfort

Results

Bythesecondtrimesterofpregnancy,ababy's heartfullydevelops,allowingforthe developmentofASD.Medicalconditions, geneticabnormalities,andlifestylefactorscan significantlyaffectorganogenesis.Screening forASDduringpregnancyiscrucial,especially ifthedefectisinherited.Smalldefectsaren't fatal,butlargeonescancauseseriousillness.

Discussion References

Atrialseptaldefectsoccurduringpregnancy duringtheformationofafetus’sorgans.The maincomponentsthatplayaroleinthe developmentofthisconditionwerefoundtobe genetics,rubella,orGermanmeasles,diabetes, lupus,alcoholortobaccouse,illegaldruguse,and useofparticularmedications.Thegenetic componentofASDmaybelinkedtopotential mutationsingeneslikeNKX2-5andGATA4. NKX2-5isinvolvedintheregulationof transcribinggenesduringmorphogenesiswhere theshapeoftissuesororgansformduring embryonicgrowth.BecausedisruptionsinNKX25transcriptionfactorfunctionsareassociated withthelackofheartdevelopmentinDrosophila melanogastermodelorganisms,furtherresearch suggeststhatitmaybeatargetoffutureresearch regardingASDsinhumans.Similarly,GATA4isa majorregulatorytranscriptionfactorassociated withheartdevelopment.Inadditiontogenetic factors,virusesanddiseasesarealsothoughtto playaroleinASDdevelopment.Maternalrubella duringpregnancywasfoundtospreadtothe placentaandfetus.Thisinfectionresultsinthe infectionofcardiofibroblaststhataremeantto assistinthebuildingoftheheart’scellular structure.Thisincludesregulatingthegrowthof embryoniccardiomyocytes,whichformthe matureheartchamber,createscaffoldingfor cardiaccellstoattachto,andoverallassistinthe growthandbuildingprocessrequiredtoformthe heart.Moreover,lifestylechoicesanddiseases, suchasunregulateddiabetes,isalsothoughtto playamajorroleinASDdevelopment. Unregulateddiabetesduringpregnancywas showntobelikelyrelatedtonearly24%ofatrial septaldiseasesintheUnitedStates.

A ra Septa Defect(ASD) AmercanHeartAssociationCPR&FrstAid EmergencyCardovascu arCare [accessed2023Aug17] https/ cprheartorg/en health-topics/congenital-heart-de ects/aboutcongenta -hear -defects atrial-septa -de ect-asd Atrialseptaldefect(ASD) MayoClnc 2022Mar1[accessed2023Aug17 https/ wwwmayoc incorg diseases-condtions atral-septal-defect/symptomscauses syc-20369715

A ra septa defect ASD)(2023)wwwheartorg Avai ab eat https/ wwwheartorg/en/health-topics/congenital-heart-defects/aboutcongenta -hear -defects atrial-septa -de ect-asd(Accessed 17August2023) Dz OM etal (2021)Personalzedgeneticdagnosisofcongenta heart de ec s nnewborns,Journalofpersona izedmedicine Avai ab eat https/ wwwncbin mnhgov/pmc articles/PMC8235407 Accessed 17August 2023)

professona CC medica nodate ASDclosure:Procedure risksand Recovery C evelandClnic Avai ab eat https/ myc evelandc incorg health treatments 22461-asd-closure Accessed: 17August2023)

UCSFHea th(2023)Minmal y nvasivec osureofatrialseptaldefect ucsfhealthorg Avalablea :https/ wwwucsfhealthorg treatments mnima lyinvasve-c osure-of-atrial-septa -defec (Accessed 17August2023) A ra septa defect ranscatheterreparforchldren(2023)JHM Avalablea : https/ wwwhopkinsmedicneorg/hea th/treatment-tests-and- herapes/atriaseptal-defect-transcatheter-repair-forchldren#: :text=ASD%20 ranscatheter%20repar%20uses%20a, olded%20up%2 0 ike%20an%20umbre la (Accessed 17August2023

AboutKdsHealth Avai ab eat https//wwwaboutkidshea thca/Artc e? contentd 1668&language Eng ish(Accessed 17August2023) professona CC medica nodateb)Atra septa defect ASD) Symptoms, causesandtreatment Cleve andClinic Avalableat: https/ myc evelandc incorg health diseases/11622-atrial-septa -de ec -asd (Accessed 17August2023

Congenitalheartdefects-factsabouta ra septa defects 2023 Centersfor DseaseControlandPrevention Avalableat https/ wwwcdcgov ncbddd heartdefects/atrialsep aldefecthtml(Accessed 17 August2023) Cause‐specifcmortaltyofpatentswthatria septa defectandup Avalableat:https/ wwwahajournalsorg do/101161 JAHA122027635 (Accessed 17August2023

Acknowledgments

Wewouldliketothankourmentor,Giovanna Napoleone,fromColumbiaUniversity,and ourexecutives,VyLy,AryanaWadhwani,and KatieKee,forprovidinguswiththeresources andknowledgethatweneededinorderto makeourprojectasuccess!

SuryaAni,ShantosmitaBiswas,VidhiPatel,KatieVo GiovannaNapoleone,ColumbiaUniversity

Deepanalysisonwhyatrialseptaldefects occurininfants

Introduction Results

Theatrialseptum,acrucialpartofheart development,canbedisruptedduring embryologicaldevelopment,leadingto ASD.Abnormalitiesintheseptum's formationorfusion,linkedtoheart developmentsignalingnetworks,cancause ASD.

TypesofASDinclude:

Secundum:Thisisthemostcommon typeofASD.Itoccursinthemiddleof thewallbetweentheupperheart chambers(atrialseptum).

Primum:ThistypeofASDaffectsthe lowerpartoftheatrialseptumand mightoccurwithothercongenitalheart defects.

Sinusvenosus:ThisraretypeofASD usuallyoccursintheupperpartofthe wallseparatingtheheartchambers.It's alsoassociatedwithotherheart structurechangespresentatbirth.

Coronarysinus:InthisraretypeofASD, partofthewallbetweenthecoronary sinus whichispartoftheveinsystem oftheheart andtheleftupperheart chamber(leftatrium)ismissing.

Largeratrialseptaldefectscausesymptoms likeright-sidedheartfailure,difficulty breathing,irregularheartbeats,heart murmurs,swelling,stroke,earlydeath,and highbloodpressure Factorscontributingto ASDincludegenetics,Germanmeasles infection,diabetes,Lupus,alcohol,tobacco, illegaldrugs,andcertainmedications.

Methods

Types of ASD

SuryaAni,ShantosmitaBiswas,VidhiPatel,KatieVo GiovannaNapoleone,ColumbiaUniversity

Secundum Primumm Sinus Venosus Coronary sinus

Transcatheter ASD Closure

Surgical Repair

Balloon Atrial Septostomy

ASD Captured in fetal ultrasound

Transthoracic echocardiography showing the process of transcatheter device closure of atrial septal defect.

Atrial Septal Defect Closure Device

Abstract

TheRoleofNeurogenesisintheCuringof

Alzheimer's SherinBiji,ManaSeto SofiaSeewald,EmoryUniversityinAtlanta,GA

Materials and Methods

As Alzheimer's remains a constant topic in medicine, researchers have been in the process of discovering and developing possible cures and preventions. Alzheimer's is a neurological disorder that slowly destroys the brain leading to the loss of memory and other functions of the brain. This paper explores the depths of whether Alzheimer's can be cured with the help of neurogenesis; the regeneration of the brain cell. The resulting implications may lead to further research and discoveries in order to cure patients and engineer technology that will innovate new openings in the field keywords: Alzheimer's, neurogenesis, genetic, cure

Introduction

Can Alzheirmers be cured via neurogenesis? Alzheimer's is a currently incurable neurological disorder that leads to the loss of memory, communication, and other mental functions (Mayo Clinic n.d). Neurogenesis is the process by which the neurons are developed. The purpose of this paper is to find out whether Neurogenesis can cure Alzheimer's

Results

Bax, a gene that causes cell deaths can be removed using genetic engineering, resulting in the person affected by Alzhemires to have better spacial recognition and contextual memory tasks As the production of new cells has proven to delay symptoms, Alzheimer's may be cured by genetically modifying the brain to produce more cells, mimicking the brain's natural process of neurogenesis.

References

years depend ng on o her factors A zhe mer s destroys one part o the brain which affects a l the other par s and gradua ly eads to a l the ce ls in the bra n dying The damage caused by th s d sease is irrevers ble (Alzhe mer s n d )

Introduct on to Neurogenes s: The process in which new neurons are made in the bra n s known as Neurogenesis This process starts from the embryo and con inues throughout ife Each part of he brain has many spec a ized neurons For example, the par that p ays an important part in memory and spat al navigation is known as the hippocampus This part has over 27 neurons that are spec a ized for the hippocampus Dur ng the process of Neurogenes s the s em cel s spec al zed cel s n d fferent parts of the bra n and at d fferent times S em ce ls can produce an inf ni e amoun of stem cel s, wh ch then turn into d fferent special zed cel s For example progenitor ce ls The progen tor cel then turns nto spec f c types of neurons Research 2018)

Treatmen for Alzhe mer s through neurogenesis

A s udy conduc ed in 2019 shows that people who are affected by A zheimer s and have more requent neurogenes s are more l kely to have ess cognit ve mpairment as new cel s develop Cogni ive decl ne and Dement a could be delayed f the brain ce ls can regenerate The same study done on mouse mode s ed by Or y Lazarov from the Universi y o I l nois Chicago discovered that the ncrease n he product on of neurons in the bra n can res ore one s memory (Sp chack 2022)

The researchers at UIC found that when the production of neurons with Alzhe mer s mutat ons was ncreased and the gene caus ng cel deaths was removed he m ce had better spatia recogni ion and contextua memory tasks These mice were also discovered to have deve oped dendr t c spine structures which p ay an important role in memory formation The neurons a so achieved o have a more normal prof le Further, when the ce ls in the mice were edited o deactivate neurogenesis the r spa ia recognit on and contextua memory worsened, demonstrat ng he importance of neurogenes s n reversing Azheimer s (F e cher 2022) Another s udy by the Massachuse ts Genera Hospital figured out hat by genetica ly ncreasing the neurons n the bra n structure where memor es are encoded, Alzheimer s-af ected mice showed mproved eve s of cognit ve unct on However the ef ects on improved cogni ion were seen to be b ocked by the env ronment hat is created by Alzhe mer s n one s brain Different phys cal exercises can he p n c ear ng these environments which w l he p n the growth o new cel s (Research 2018)

Imp icat ons and further stud es

Further research should be conducted to ind the extent o wh ch neurogenes s and gene edi ing can retract or delay symptoms and to deve op poss ble technology and / or medicat on that s safe for human use n order to re rac symptoms

L m tat on:

This pro ect is archival research and mere y a co lec ion of mp icat ons gathered from exist ng sources There were also l m tat ons n he avai abi ity of free access ble sources

Fletcher L UIC sc ent sts d scover method for restor ng memory oss from A zhe mer s disease UIC Today [Internet] 2022 Aug 19 [updated 2023 Aug 17; c ted 2023 Aug 17] Ava lab e from: https:/ today uic edu/u c-scient sts-discovermethod-for-restor ng-memory- oss-from-a zheimers-d sease/ Research Study Finds Neurogenesis Can He p Improve Cognition Function n Mouse Model of A zheimer s The Hearing Rev ew [Internet] 2018 Sept 12 cited 2023 Aug 16 Avai able from https //hearingrev ew com/ins dehearing/research/research-study-f nds-neurogenes s-can-he p-improve-cogn tivefunction-mouse-model-alzheimers

Spichack S Neurogenesis: He ping the Bra n Grow New Cells in A zheimer s Beingpatient com [Internet 2022 Feb 24 [c ted 2023 Aug 16] Availab e from: https //www be ngpatient com/neurogenes salzheimers/# :text=These%20findings%20came%20w th%20an,did%20in%20fact %20improve%20cognition

What s Alzheimer’s Disease? A zheimer s Association [Internet] Ava lab e from: https //www alz org/alzhe mers-dementia/what- s-alzheimers

What s Neurogenes s? Queens and Austra ia: The University of Queensland Queensland Brain Inst tute [Internet] Available from https: /qbi uq edu au bra nbasics/brain-physiology/whatneurogenesis# text=Neurogenesis%20is%20the%20process%20by,birth%20and %20throughout%20our%20lifespan

A zhe mer [Internet] Mayo Clinic [c ted 2023Aug 16 https //www mayoclinic org diseases-conditions/alzheimers-disease symptomscauses/syc-20350447

Ear y-Onset Dementia and Alzheimer Internet] February 27 2020 Blue Cross Blue She ld [cited 2023Aug 16] https://www bcbs com the-health-ofamer ca/reports/early-onset-dementia-alzheimers-disease-affecting-youngeramer can-adults

Acknowledgments

We thank the TRC executives and mentors for providing us with this research opportunity, as well as our mentor who reached out with her support, and our team members who have contributed to this project.

(Early-Onset 2020)

The sources for this research have been consolidated from Medical review Organizations, University Articles, and others using Google's common research tool Google Scholar through a meticulous process of filtering, to obtain concise and relevant papers and articles that contribute to solving the questions that were proposed.

EvaluatingtheApplicationofExosomesinDisease Immunotherapy

R.Sleimna,J.Chan,N.Yam

S.Seewald,EmoryUniversityinAtlanta,GA

Abstract

Exosome-based immunotherapy has many methods to its implementation.in this research paper we will be discussing exosome isolation, characterization and immunotherapeutic strategies for some diseases advatages and disadvantages and even in vitro and vivo experiments and the results of some clinical trials

Introduction

Exosomes in immunotherapy In addition to exosome-mediated delivery of anti-cancer drugs to target cancer cells, exosomes can be used in immunotherapy to achieve a sustained and specific immune response against cancer cells Exosomes can present tumor antigens to dendritic cells (DC cells) and promote DC maturationDue to their nano-size (30–150 nm) and biological functions, exosomes have been used as nano-carriers for small molecules and macromolecules (siRNA and pDNA) in cancer therapy in preclinical studies, as well as biomarkers for cancer diagnosis and prognosis

Results

Materials and Methods

According to the title of this experiment, an outline of main components constituting to the applicability of exosome-based therapy was developed In which extensive research was conducted according to th following subtopics

Exosome Isolation and Chategrizaiton

Exosome Loading and Modification

Immunotherapeutic Strategies

In Vitro and In Vivo Experimentation

The above subtopics aim to encapsulate both the procedure of exosome study and utilization, and to pinpoint the main areas in which constitute greatly to the applicability of the vesicle in disease therapy.

Fig A:

Showing the percentage of clinical trials conducted, utilizing exosome based bio-markers, of which cancer is the most prominent at 74 13%

Analysis of exosome-based biomarker clinical trials

Fig 1: Survey results from ClinicalTrials.gov on the major applications of exosomes

Results show the most prominent application of exosomes to be biomarkers, being followed by exosome therapy, for analytical use, as a drug-delivery systems and cancer vaccines

Fig B:

Showing the respective amounts of clinical trials conducted on different diseases using exosome based biomarkers , of which trials regarding lung cancer have been conducted most (>12 trials)

Fig C:

Showing the respective amounts of therapy based exosome trials for different diseases, of which SARS Cov2 Pneumonia holds most prominence at ~9 trials

The Advantages and Disadvantages of different exosome separation technologies

Analysis of exosome-based biomarker clinical trials (A, B) and exosome therapy-based clinical trials for different diseases (C)

EvaluatingtheApplicationofExosomesinDisease Immunotherapy(cont.)

R.Sleimna,J.Chan,N.Yam

SoifaSeewald,EmoryUniversityinAtlanta,GA

Discussion

Exosome drug loading strategies include incubation, electroporation, sonication, freeze–thaw cycle, transfection, extrusion, chimeric exosome method, and endogenous loading Different methods need to be performed under different conditions and the drug loading efficiency of exosomes depends on different loading methods

Conditions of drug loading, loading efficiency, and

Conclusion

The potential of exosomes in immunotherapy is essentially the effect of Exosomes in the Regulation of Immune Responses: The transfer of exosomes between immune cells can have a strong functional effect on immune responses and either promote, deviate or suppress immune responses As we have discussed the isolation , characterization, Advantages and disadvantages and much more the fate of exosomes based immunotherapy is looking bright

Acknowledgements

The authors would like to express their gratitude towards all authors of the journals and articles both referenced and cited, the mentor of our group for her guidance and support, all members for their contribution and last but not least the members of TRC for this wonderful and eye-opening opportunity.

References

Pharmaceut cs 2019 March 25; 16 (6) 2309-2314; do :

Prospects for future modifications

future research will be needed to explore potential modifications on exosomes

Topics of future research extending on current data include:

constructing exosomes to specifically serve drug delivery and clinical efficacy

alternative drug delivery options

predictions of exosome long-term safety and efficacy

exploring methods to safely and effectively anchor targeting peptides on exosomes is still a problematic issue

10 1021/acs molpharmaceut 8b01093

L u C, Su C Des gn strategies and app icat on progress of therapeut c exosomes Theranostics 2019 Jan 30;9(4):1015-1028 do :

10 7150/thno 30853 PMID: 30867813; PMCID: PMC6401399

B oMed Centra [Internet] Isolat on and characterization of exosomes for cancer research - Journal of Hematology & Onco ogy; [cited 2023 Aug 17] Available from: https:/ jhoonline biomedcentral com/artic es/10 1186/s13045-020-00987-y

B oMed Centra [Internet] A review on exosomes applicat on in cl n cal tr a s: perspective questions and cha lenges - Cell Communication and Signaling; [c ted 2023 Aug 17] Ava lable from: https://b os gna ing biomedcentra com articles/10 1186/s12964022-00959-4#Sec6

Chaput N Taïeb J, Schartz NE, André F, Angev n E, Zitvogel L Exosome-based mmunotherapy Cancer Immunol Immunother 2004 Mar;53(3):234-9 do : 10 1007/s00262-003-0472-x Epub 2004 Jan 16 PMID: 14727085

Fu S Wang Y, Xia X, Zheng JC Exosome eng neering: Current progress n cargo loading and targeted del very, NanoImpact, Vo ume 20 2020 100261 ISSN 2452-0748 https://do org/10 1016/ impact 2020 100261

Gangadaran P, Madhyastha H, Madhyastha R Ra endran RL, Nakajima Y Watanabe N Velikkakath AKG, Hong CM Gop RV Muthukalianan GK Valsa a Gopa akrishnan A Jeyaraman M, Ahn BC The emerging ro e of exosomes n innate immunity diagnos s and therapy Front Immunol 2023 Jan 16;13:1085057 doi: 10 3389 fimmu 2022 1085057 PMID: 36726968; PMCID: PMC9885214

Hu K McKay PF, Samnuan K, Najer A, B akney AK, Che J, O Dr sco l G, C hova M, Stevens MM Shattock RJ Presentation of ant gen on extracel ular vesicles using transmembrane domains from vira glycoproteins for enhanced immunogen city J Extracell Vesicles 2022 Mar;11(3):e12199 doi: 10 1002/jev2 12199 PMID: 35233930; PMCID: PMC8888812 Hussa n MWA Jahang r S Ghosh B Yesm n F An s A Sat l SN Anwar F Rashid MH Exosomes for Regulation of Immune Responses and Immunotherapy Journal of Nanotheranostics 2022 March 16; 14(1):55-85 https://doi org/10 3390/jnt3010005

Exosomes

mod fications, and therapeut c appl cations European Journal of Medicinal Chem stry, 207 112784 https://doi org/10 1016/

different

GREEN COMPUTING:

Abstract

Thisstudyexploredtheapplicationsofgreencomputinginbusinessoperations, whilsttakingintoconsiderationthelegislativeactionstobemadeorimprovedupon toensuregreencomputingsucceeds.Currentmarketsforcomputingcorporations contributetotheclimatestressesthroughpoorchipandsystemdesignthatwastes materials.Byexploringtheideaofgreencomputing,companiescanincrease efficiencyintheworkplaceandcutbackonmanufacturingcosts-protectingthe environment.StartingwithEnergyStarlaunchedbytheEPAin1992,green computingwasintroducedtothecomputingworld,savingbillionsincoststhrough energyefficiency.Morechipshavebeenredesignedtomirrorthis,aswellasusing materialsthataregentleontheenvironmentandlastlonger.Theseresultswarrant legislativeactionstosolidifythefutureofcomputinginasustainableframe.

Introduction

Theprimaryfocusofthisstudyistoidentifytheintersectionofgreencomputing andbusinessoperations,harpingontheimpactenergyefficienthardwarehason companyprofitabilityandenvironmentalhealth.Problemswithrecentcomputing trendsconsistofhardwareinefficienciesthathinderbusinessprocessesandleadto greaterenvironmentaldegradationthroughharvestingmaterials.Throughgreen computing,ithasbeenfoundthatbusinessescanactuallycutbackcostson manufacturingwhilstalsooperatinginasustainableway.Thisprompted discussionsoflegislativeactionsnecessarytomakegreencomputingan expectationinmoderncomputing.

Methods and Materials

Environment:ResourcehungrysoftwaredemandsforfasterCPUsleadingtothe needfornewercomputerhardware.Thiscreatesanendless,wastefulcycle(2). Anotherexampleofthisismostchipdesignsareoptimizedforsize,performance, andbatterylife.Despitethechiphavingabout100squaremillimetersofsilicon, it’sgreatlyinefficientasonlyaportionofitisactuallyutilizedinelongating batterylife,leavingtheresttowaste.Additionally,thetechnologyindustry (ICT)’s estimatedcontributiontoglobalcarbonemissionisbetween1.8to3.9%(7).

BusinessOperations:ThoughprofitabilityishigherintraditionalIT,the operationalcostsarehigherthanprofits.GreenIT,ingeneral,notonlyhaslower operationalcostsbutalsoyieldsahigherpercentageofprofitabilityincomparison tothecost.(refertoFig2.)

ComputationalScience:Greencomputingcanbeseenthroughtwolenses(refer toFig1a) Furthermore,useofgreentechnologyincomputationalsciencevaries onthespecificsector.Itshouldbenotedthatpowerprofilinghastheleastgreen technologyadoptionwhereascloudcomputingandvirtualizationhasthehighest adoption(refertoFig1b.)

References

The Impact on the Environment, Business Operations, and Computational Science

Discussion

Surprisingly,traditionalcomputingisthoughttocauseminimalenvironmental impact,however,thesepracticesarequiteharmful.Unfortunately,theresults expressthatmanycorporationsfocusonefficiencyanddisregardthe environmentalproblemscaused.Itiscrucialthatenvironmentaleffectsare consideredastheelevationofcarbonemissionscanleadtoaclimatecrisis,hence foodshortages,andeventuallymassextinction(11).Onesolutionthatthisstudy investigatedwasgreencomputinganditsinfluenceonbusinessand computationalscience.GreenITminimizesthedamagingeffectsonthe environmentbydesigningenergyefficientchips,buildingsoftwarethatdoesnot relyonexceedingamountsofCPU&GPU,andcreatingtechnologyfromnon harmfulmaterials(10).Furthermore,greentechnologyalsooptimizesprofitsfor businesses(Fig2).However,toguaranteethatenvironmentalconcernswill becomeanimportantfactorinbusinessdecisionmaking,legislationisnecessary. Forinstance,theGreenActof2021offersfiveyearsoftaxcreditforthe installationofrenewableenergyfacilities(4).Similarly,taxcreditforacertain amountoftimecanbeawardedforimplementinggreentechnologies.The ratificationofagreenenergybillforthetechnologysectorpermitsrecordingdata ontheemissionsproduced,thus,highlightswhoreleasesexcessiveamounts. Theseextremeproducerswillfacefines.Nonetheless,thisstudy’smain limitationistowhatextentcantaxcreditberewardedandifit’llbeenoughto persuadebusinessestochangetraditionalmethods.Inthefuture,researchers shouldexplorehowmuchtaxcreditisallowedtobegivenandexpandupon morewaystoeasilyinstallgreentechnology.

Results

Thecorrelationbetweengreentechnologyadoptionandthe50%decreasein operatingcostsaftertheimplicationofGreenITpracticesshowcasesthatgreen technologyisalessexpensivealternativetotraditionalIT.

Thewasteproducedfromunusedchipsandoutdatedcomputerhardwareislinked totheestimated1.8%to3.9%ofglobalcarbonemissionsproducedfromICT.

TherelationshipbetweentraditionalITpracticesand1.8%to3.9%ofglobal carbonemissionscausedbyICT.

Acknowledgements

Theoverallverdictisthatgreencomputingbenefitsnotonlytheenvironment, butalsothedesignandmanufacturingofsoftwareandhardwareusedin computationalscience.Businesseswhohavealreadyincorporatedgreen technologyearnahigherpercentageofprofitability.Thesefindingsdemonstrate thatthetechnologysectorcanaidinreducingglobalcarbonemissionsandno longerbepartoftheproblem.

Many thanks to TRC (The Research Catalysts) for their guidance throughout the research process and to our mentor Prince Tufon for his valuable insights regarding direction in this literature review.

Arushi Dashore, Renee Cargill, Hayat Farah Prince Tufon, Massachusetts Institute of Technology

Fig 1a.

Fig 2.

Fig 1b.

References

1) Agarwal S., Basu K., NathA. Green Computing and GreenTechnology based teaching learning and administration in Higher Education Institutions, online journal, 2013 Sept.

2) Agarwal S., NathA., Chowdhury D., SustainableApproaches and Good Practices in Software Engineering, online journal, 2012.

3) Burrows L. Smaller, Faster, Greener. Cambridge: Harvard School of Engineering andApplied Sciences; 2021.

4) Congress, H.R.848: Growing Renewable Energy and Efficiency NowAct of 2021 or the GREENAct of 2021, 2021-2022.

5) Dziurzyński, D. How is Green ITshaping the software development industry?, website, 2023.

6) Everest Global Inc.,The Environment’s Calling: Sustainable SoftwareApplication Development Is the Need of the Hour, website, 2021.

7) Knowles B.ACMTechBrief: Computing and Climate Change. Lancaster:ACMTechnology Policy Council; 2021.

8) Merritt R., What Is Green Computing?, website, NVIDIA, 2022

9) Salama M. Green Computing, a Contribution to Save the Environment. Lancaster: Lancaster University; 2020.

10) What is Green Computing?.Armonk: IBM; 2022.

11) With New Climate Pact,Tech CompaniesTake on Climate Change. Nairobi: UNEP; 2021.

12) Zajer M. Green Coding:The Secrets to Unlocking More Sustainable Software Engineering, website, 2022.

TheApplicationsandEthicsofCRISPR-Cas9

AngelaDong,KalieHuynh,JustinPham,ChristinaUong SeanMintz,MIT

Abstract

Cluster regularly interspaced short palindromic repeats-associated protein 9, also known as CRISPR-Cas9, has emerged as an innovative instrument in the realm of biotechnology. This review explores the chief elements of Cas9 and sgRNA that drive the technology and its ways of delivery of microinjection, electroporation, and vector methods. This discovery has opened up vast and transformative applications in various fields, such as medical advancements in numerous diseases, medicinal supplements, and the food industry. However, with this comes its ethical considerations. Its capability to delete, correct, and insert new genes raises complications in human genetics, where professionals can edit certain genetic traits or diseases in human embryos. This research investigates the mechanisms of CRISPR-Cas9 and its controversial implementations.

Introduction

First introduced in 2012, CRISPR-Cas9 is a gene editing tool that has gained popularity in the gene-editing world for its preciseness and efficiency. Being a versatile tool that can practically edit any segment of DNA, it can be applied to all sorts of problems, the largest being treatment for human cancer and diseases. As its applications continue to develop, ethical concerns and issues arise about its safety and potential exploitation.

Materials and Methods

Gene-editing process: CRISPR-Cas9 consists of two main components: Cas9 (a protein) and sgRNA (single-guide RNA). The sgRNA guides Cas9 to locate and produce a double strand break (DSB) on the targeted DNA strand near a PAM site (a location on the DNA strand with the sequence of NGG). The DSB is then repaired by mechanisms, such as homology-directed repair (HDR), which uses a template to precisely repair the DSB. The product of this modification results in gene knock-in, correction, deletion, or mutagenesis.

Some CRISPR-Cas9 delivery methods:

Microinjection - This method physically injects Cas9 protein and the sgRNA directly into individual cells using a needle and microscope. Best for in vitro and ex vivo.

Electroporation - This method uses electrical currents at a high voltage to open pores in the cell membrane of cells, allowing CRISPR-Cas9 components to travel into the cell. Most commonly used for in vitro, but can be used for ex vivo as well.

Vector methods (Viruses: AAV, LV, AdV) - This method involves vectors (modified viruses) that are particles containing CRISPR-Cas9 components which are used to infect the target cells.

TheApplicationsandEthicsofCRISPR-Cas9

AngelaDong,KalieHuynh,RuhiKamdar,JustinPham,ChristinaUong SeanMintz,MIT

Results

CRISPR-Cas9, a gene editing tool, has led to greater development in both the medical and agricultural fields because of its ability to alter DNA sequences. Progress has been made in correcting genetic mutations so that fetuses who would have been born with them can live a normal life. Cancer and other diseases stemming from the mutation of DNA can be reversed. Engineered crops can provide food security, while being easier to produce and tastier. CRISPR-Cas9 can also improve pharmaceutical medicines by increasing the potency of ingredients. However, the side effects of CRISPR-Cas9 should not be neglected. As the technology is still immature, gene editing may also cause consequences that have not been fully understood yet. Additionally, there is a chance of CRISPR-Cas9 modifying DNA at other locations instead of the intended target, leading to harmful genetic changes. Future generations may also have unforeseen health issues due to gene editing. Even so, there is ongoing research towards addressing these challenges and striving for safer and more precise gene editing techniques to minimize side effects, enhance accuracy, and guarantee a more responsible and ethical application for the future. CRISPR-Cas9 has the potential to eradicate genetic diseases and gain a surplus of food which can result in a thriving society with improved quality of life for all.

Discussion

Despite CRISPR-Cas9 having multiple technological advancements and breakthroughs, it has also raised questions about legal, social, and ethical rules. Because CRISPR-Cas9 has the ability to edit genetics from a single cell to a whole organism, it can be used to treat cancer or neurodegenerative disorders, create allergy-free foods, or even manage diseaseridden insects. However, this technology also has the ability to also genetically edit the human embryo before it is born. For example, if the embryo has some sort of genetic disease such as sickle cell anemia or cystic fibrosis, CRISPR would technically have the ability to rid the embryo of those diseases, while still in the birthgiver’s belly. Depending on what types of genetic diseases the embryos have and the severity of them, these types of practices have started debates on what can blur the line between enhancement and treatment/therapy because scientists acknowledge that genetically altering embryos before birth can be weaponized for eugenics and other negative/harmful ethical/moral beliefs as well. In addition, CRISPR’s genetic editing on embryos can cause harmful side effects, so even if CRISPR is being considered, scientists and other healthcare professionals will still be looking for safer alternative methods.

TheApplicationsandEthicsofCRISPR-Cas9

AngelaDong,KalieHuynh,RuhiKamdar,JustinPham,ChristinaUong SeanMintz,MIT

SeanMintz,MIT

References

Carney JP, Harper JC, Lino CA, Timlin JA. Delivering CRISPR: a review of the challenges and approaches. Drug Delivery. 2018 Feb 12;25(1):1234-1257.

Del Rio A, Marinelli E, Piergentili R, Signore F, Umani Ronchi F, Zaami S. CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues. Cells. 2021 Apr 21;10(5):969-992.

Doudna JA, Jiang F. CRISPR-Cas9 Structures and Mechanisms. Annual Review of Biophysics. 2017 Mar 30;46:505-529.

Hamideh AA, Hosseinkhani S, Khoshandam M, Mousazadeh M, Soltaninejad H. Clinical applications of the CRISPR/Cas9 genome-editing system: Delivery options and challenges in precision medicine. KeAi Publishing. 2023 Mar 26;11(1):268-282.

Khlidj Y. What did CRISPR-Cas9 accomplish in its first 10 years? Biochem Med (Zagreb). 2023 Oct 15;33(3):030601

Acknowledgements

We thank The Research Catalysts for giving us this opportunity and their guidance along the way. We also thank Sean Mintz, our mentor, for providing us feedback and assistance through our entire research process.

HOWCANRECENTADVANCEMENTSINBIOELECTRONICSHELPPROVIDE

BETTERENERGYSUPPLYANDIMPROVEDLONG-TERMDEVICEEFFECTIVENESS?

StevenBiji,SiddhTolia,SophieNguyen,AizaTanveer SeanMintz,MassachusettsInstituteofTechnology

Abstract

Organic Bioelectronics is the development and study of organic electronic devices which translate the signals and functions of biology and use organic electronic materials to conduct biosignals

It was observed that Bioelectronic devices have a critical challenge in sustaining energy during it's operation Solutions include: Supercapacitors, Internal Energy Harvesting Devices, Biofuel Cells, and Wireless Power Transfer. A change in materials, energy harvesting, supplies, data transmission, and more can improve biocompatibility with bioelectronics.

Key Words:Organic bioelectronics,implantable devices, biocompatibility,energy storage

Introduction

This academic paper explores the rapidly developing field of Organic Bioelectronics for Healthcare, specifically devices that promote improved treatment methods, and overall health of a person. Through a thorough analysis and synthesis of the latest research findings, the paper takes into account critical factors such as energy supply and biocompatibility in these bioelectronic devices Our meticulous review of pertinent publications has yielded a comprehensive understanding of the current state of Organic Bioelectronics and its

potential for transforming healthcare

Our objective is to contribute to the ongoing discourse on this topic and provide valuable insights for researchers and practitioners alike

Materials and Methods Discussion

Organic bioelectronics comprises the development and studies of organic electronic devices that operate as translators between the signals and functions of biology. These devices use organic materials that can conduct and process electronic and ionic biosignals, used with an electron-ion charge compensation(a slow discharge of ions, resulting in electrical potential). The use of these styles of devices in electrocardiographs, blood pressure and flow monitors, medical imaging systems, etc., has been done for a long period, although recent advancements have further improved these devices and solved two of the numerous problems faced since their conception: Energy Storage and Biocompatibility. Both of these are further described in this paper.

( Simon, D.T., 2016)

Summary

The realm of organic bioelectronics offers a plethora of innovative solutions fueled by the convergence of organic electronic materials with biology and medicine This paper delves into the remarkable capabilities of bioelectronic devices and shows some of the recent developments that answer some pressing problems the application of these devices faces while being used in the field of medicine By making changes to the biocompatibility and technological structure of bioelectronics, it is supported that these devices are significantly effective long-term and contain better energy supply These findings present that the utilization of materials, supplies, and other resources can improve bioelectronics by making them more biocompatible (Yang Li, 2021)

Section1:Problemsintradtionaldevices

Bioelectronic devices face a critical challenge in sustaining energy during operation This section explores problems in conventional devices and what factors are needed to account for sustainability and compatibility of these devices.

Flexibility, biocompatibility, and stable energy density are crucial to power these devices effectively Traditional Li-ion batteries can be problematic due to hazardous components and packaging requirements. Moreover, implantable devices, which rely on rigid silicon microelectronics, encounter challenges related to poor compatibility with biological systems and high invasiveness. In order to be effective, bioelectronics needs to be physically and chemically biocompatible. Sustainable power supplies and wireless data transmission under implantation can be adequate Recent projects are looking to mimic the mechanical properties of tissues through materials, devices, power source technology, and wireless communication

Section2:ProposedAlternatives

This section explores recent innovations tackling this issue and categorizes them by type and application,offering a historical context of the field's progress

Promising solutions include utilizing body fluids as electrolytes for Supercapacitors,resulting in stable potential and cyclic stability

Internal Energy-Harvesting Devices harness body fluids,temperature gradients,and chemical energy for power generation

Biofuel cells, as external Energy-Harvesting Devices, convert biochemical

reactions into electricity They hold the potential for sustained energy production over time.

Wireless Power Transfer (WPT) Technology eliminates wiring needs, reducing device size and weight WPT method has a high transmission efficiency greater than 80%.

Ultrasound-Induced Wireless Energy Harvesting (UWEH)

converts ultrasound waves into power through piezoelectric- semiconducting coupling

Hydrogels (with their loose three-dimensional network structure that encapsulates massive amounts of water) can achieve a unification of excellent properties such as mechanical properties, self-healing, adhesion, and biocompatibility, making them suitable for health monitoring bioelectronics.

Future research will need to be conducted in order to engineer satisfactory material that provides long-term stability, biocompatibility, and sustainability. In conclusion, innovative energy solutions are transforming bioelectronics, enabling more efficient and sustainable device operation

References

1.Sheng, H. et al. (2021) Recent advances of energy solutions for implantable bioelectronics, Advanced healthcare materials. Available at: https://pubmed.ncbi.nlm.nih.gov/33930254/ (Accessed: 14 August 2023).

2. Li, Y.et.al, Implantable bioelectronics toward long-term stability and ... - cell press, Science Direct. Available at: https://www.cell.com/matter/pdf/S2590-2385(21)00056-4.pdf (Accessed: 18 August 2023)

3. Malliaras, G. and McCulloch, I. (2023) Introduction: Organic bioelectronics | chemical reviewsACS publications, ACS Publications. Available at: https://pubs.acs.org/doi/10.1021/acs.chemrev.2c00026 (Accessed: 15 August 2023).

4.Simon, D.T., et. al, Organic bioelectronics: Bridging the signaling gap ... - ACS publications, ACS Publication. Available at: https://pubs.acs.org/doi/10.1021/acs.chemrev.6b00146 (Accessed: 18 August 2023).

5. Li, Y. et al. (2021) Implantable bioelectronics toward long-term stability and sustainability, Redirecting. Available at: https://doi.org/10.1016/j.matt.2021.02.001 (Accessed: 18 August 2023).

6. Zhou, Y., Liu, C. and Huang, Y. (2020) Wireless power transfer for Implanted Medical Application: A Review, MDPI. Available at: https://doi.org/10.3390/en13112837 (Accessed: 18 August 2023).

7. Hua, J. et al. (2023) Hydrogel-based Bioelectronics and their applications in health monitoring, MDPI. Available at: https://doi.org/10.3390/bios13070696 (Accessed: 18 August 2023).

Acknowledgments

We would like to thank the Program Executive's Katie, Vy, Aryana for organizing this well-organised research program. We would also like to thank our mentor Sean Mintz, who gave us guidance throughout the whole program. We would also like to thank all the contributors of the paper for their invaluable effort and time spent in contributing to the field of Science.

TheEffectsofChildhoodTraumaontheDevelopmentoftheBrain

Abstract

Thelastingeffectsofchildhoodtraumaonthe compositionanddevelopmentofthebraingreatlyimpact thelivesofthosewhoexperiencedsuch Traumaisoneof thecontributingfactorsthathaveahandinthe developmentofmentaldisorderssuchasPost-Traumatic StressDisorder(PTSD) Butacertaintypeoftraumahas beenoftenoverlookedinsignificanceandimportance. ThatisChildhoodtrauma.Childhoodtraumaisclassified asdevelopedtraumaobtainedthroughone'sexposureto adverseeventsintheirchildhood.Accordingtothe NationalInstitutesOfHealth,Childhoodtraumais associatedwithdevelopingmentaldisordersthat negativelyaffectone'sadultlife.Thus,anin-depth analysisoftheeffectofsuchtraumaonthedevelopment ofthebrainisrelevantsothatsolutionstosuchtrauma canbeobtainedshortly.

Introduction

AccordingtotheCentreForAddiction&Mental Health(CAMH),Trauma“isatermusedtodescribe thechallengingemotionalconsequencesthatliving throughadistressingeventcanhaveforan individual.”Inotherwords,itisanemotional responsetoanadverseevent,suchasrape, molestation,death,etc(APA,nd) Ontheother handchildhoodtraumaistheemotionalresponseto anadverseeventthattookplacewithinyour childhood.Duringsuchanevent,thebrain experiencesachangeinitsoriginalstructure,which thencausesthedevelopmentofmentaldisorders. PTSDcanbecharacterizedasaneuropsychiatric disorderthatcausesintenseorprolongeddistressat afactorthatresemblesatraumaticexperiencethat anindividualhasexperienced PTSDinthecontextofinfantsandadolescentswill becategorizedasanyadverseorextremereactionto beingexposedtoanoccurrencethatissimilartoany traumaticeventthatthechildhasexperienced

MaterialsandMethods

Therearemanynegativeencountersthatachildmay experiencethatwillresultinmaladaptiveinfantmentalhealth andbraindevelopment,but“sexualtraumaandchildhoodabuse maysimplybethemostcommonlyencounteredseverely aversiveeventsinherentinourculture”(Sirven&Glasser,1998, p.232) Theseeventshavebeenstudiedandresearchedinorderto discoverthedirectlinksbetweencertainchildhoodtraumasand latereffectsinlife AstudyconductedbyMatthiaGuntherin 1960observednewbornsandinfantsbetweentheagesof0-6 months,keepingnoteofeventsinthechildren'slivesandtheir followingbehaviorsandactionsasanimmediateresultofthe events;astheinfantsmatured,theirbehaviorsandresponses werealsodocumentedandcomparedbasedonthedifferent circumstancesininfancy Acommonconnectionbetweeninfants whoexperiencedtraumaisthelaterexperienceofPTSD Inastudy(Gilbertson2010),a"case-controldesign"wasusedto examineapairofmaletwins OnetwinwasaVietnamcombat veteran,andtheothertwinhadnoexposuretocombat Itwas laterobservedastowhichtwindevelopedPTSD andhowthe hippocampalvolumeofthetwinwithPTSDdifferedfromthe twinwithoutPTSD

Discussion

Thesestudiesdisplaythatinfantscanexperiencemany traumasthatleadtoPTSDorlaterfearswhile maturing.Inadultpsychopathologies,PTSDistheonly onethatcanbedirectlylinkedtoearlychildhood trauma PTSDcanimmediatelyimpactachildthathas experiencedaseriouslytraumaticexperiencebutalso canmanifestlaterinadulthood,especiallyinchildren thatweresubjecttoanymannerofabuseintheirearly years.Becauseinfantsareinthepredisposedcareof theirparents,itcanbethoughtthatnegativetreatment inducedbycaregiversisthemostdetrimentaltoan infantcomparedtoanyothersociallyorphysically inducedstress.Anotherpotentialstressorthatinfants canexperiencehappensduringtheagesofzerototwo months,inwhichalotofnewbornsexperiencepainful medicalprocedures

References

Results

InFreud’slastwork(1940) heobservedthattraumaearlyinlifewaseven moredetrimentaltoinfantsas“theego isfeeble,immatureandincapableof resistance.”Inmorecontemporaryterms thiscanbeinterpretedasnoticing thatthe mmaturebrain sinastateofrapddevelopmentandthereforeis muchmoresusceptibletoadversefactorsindevelopmentandgrowth Itisa matterofdebateaboutwhetheranewborncanregisterorremembera traumaticevent butdatacanshowthatthisispossible althoughthememories maybeprimitive ResponsessimilartoPostTraumaticStressDisorder(PTSD) canbedispayedwhenaninfantshowsanadversereactiontoaninfluencethat inthepastelcitedanegativeeffectontheinfant Infanttraumaresponsesand subsequentmemoresfromtraumascanbeobserved(Gunther1960)whenan infantexperiencedananoxicairwayobstructionduringfeedng,andthenwould laterbeopposedtobeingputtothebreast Thehippocampusislocatedinthe backofthebrainandisconsideredthe“learningcenter,”bymany Research (Gilbertson 2010)showsthatinindividualswhohaveexperiencedsevereor repetitivetrauma,thehippocampusislessactveandsmallerthannormal In childrenespecially,thistraumawillbedetrimentaltothematuringofthe undevelopedbrain,andthusresultinabnormalaspectsofthebrain

Thereisnowagreementthatrepetitive,sustained emotionalabuseisatthecoreofchildhoodtrauma (O’Hagan,1995) Inthecontextofneurobiological studies,theimpactsofchildhoodtraumasarearelative breakthroughconcerningthedevelopmentofchildren andtheirbrains. Manystudieshavebeenconductedinthefieldofinfant mentalhealthanddevelopment,andhaveconcluded thatthereisgreatimportanceinpositiveinfant-mother attachmentintheearlystagesoflife,andnegative reinforcementorchildneglectorabusecanleadto manyissuesinthedevelopmentofthebrain.Modern neurosciencehasproducedmoreresultsthatfocusnot justonthepathologicalprocessesofamaturebrain,but alsoontheearlydevelopmentalfailuresofthebrain. Itcanthereforebeconcludedthatnegativeexperiences inearlychildhoodoftenleadtodevelopmentinthe brain,andlaterdisordersinadulthood Whenthebrain isnotfullydeveloped,itisevermorevulnerableto distressingexternalstimuli.Evenintheearlieststages ofinfancy,thebraincanrememberandinterpret traumaticevents,whichwillcauseaneffectonthechild notonlyduringgrowthbutalsowellintoadulthood.Itis ofgreatimportanceforchildrentobeinahealthyand nurturingenvironmentwithsupportiveandinvolved caregivers,astraumaisnotsingularlyanegative interaction,butalackofinteractionaswell.

Acknowledgments

IwouldliketothankallofthewonderfulpeopleatThe ResearchCatalystswhohelpedtomakethisproject happen.Additionally,toallthepeopleinmygroup helpedtoresearch,write,andformatthispaper. MostofallIwouldlovetothankmyfriendsand teacherswhohavesupportedmeinanythingIhave wantedtopursue.Morespecifically,Iowemanythanks toSavannahFinn,whoallowedmetoattendmeetings forTheResearchCatalystsProgramwhilewewere togetherandsupportedmeonthisjourney.Finally,a largeandgratefulthankstoJennyBoehlke,forinspiring metofurtherpursuescienceandkeepmeinterestedin whythingsoccur Iwouldnothavefinishedwritingthis paperwithoutallofthepeopleaforementioned,andI amveryhonoredtohavebeenabletobeapartofthis endeavour.

JosephineMonette(Author)LakewoodHighSchool,AghoghotoboreOghenekaro(Author)GlenBurnieHighSchool

AryanaWadhwani(Mentor),KatieKee(Mentor)BreaOlindaHighSchool,VyLy(Mentor)UCBerkely

TheBehavioralChangesofConvictedFelonsBeforeandAfter Imprisonment

ShifaMalik,UniversityofMichigan

Abstract

Thepsychologicalandneurologicaleffects imprisonmenthasonanindividualcanresultin detrimentalmentalhealthoutcomes.Toprocure theeffectsimprisonmenthasonthosewhoare incarcerated:

Intensivesearchonarticlesandpapersensured thevalidityofinformation Studyingsurveys,interviews,andexperiments togatheradequatedata.

Studieshaveshownthestatusofprison confinementleadstodepressionandthedecline inmentalhealthhascontributedtotherepeating ofcriminaloffenses.Theclaimofprisonbeinga correctivemeasureforfelons,hasbeenrepeatedly falsifiedbaseduponthenegativepsychological effectsitburdensmanyprisonerswith.

Introduction

Theinformationandresearchprovidedwill delveinto:

Psychologicaleffectsprisonhason convictedfelons

Howthebrainchangesfrombeforetoo afterimprisonment.

Neurologicaleffectsconfinementhason therecipient.

Thementalhealthofindividualsafterserving prisonisupforquestion.Doestheinstitution intendedtopunishbutalsocorrectthe behaviorsoffelonsleaveapositiveimpacton theirmentalstatus,ordoestheirmental healthdecreasebasedontheharshnatureof prisonconditions?

Theresearchconductedexploresthe outcomesprisonhasonthementalhealthof formerprisonersandhowitimpactstheir dailylifebackinsociety.

MaterialsandMethods

Inthemethodssectionoftheresearchproject,a detailedstudyofarticlesandinformationavailableon thebehaviorofconvictedfelonswasconducted

Thisinvolvedasystematicapproachtogather relevantdataandinformationfromvarious academicjournalsandonlineliterature

Additionally,utilizedvariousresearch methodologiessuchasstudyingsurveys, interviews,experimentsandtogatherprimary dataonthetopic.

Bycriticallyreviewingandsynthesizingexisting studiesandinformation,afoundationwas establishedtocontextualizeandinformthe researchobjectives.

Thismethodologicalapproachprovidedasolid foundationfortheresearchproject.

Theaimwastocomprehensivelyexplorethe subjectmatterbycombiningexistingknowledge andnewinsights.

Results

Rehabilitationprogramsimplementedwithintheprison systemplayacrucialroleinpromotingpositivebehavior changeandreducingrecidivismrates.Duetolackof mentalhealthafterrelease,itmayleadtoex-felons relapsing

Theseprogramsfocusoneducation,vocational training,mentalhealthservices,andsubstance abusetreatmentfromex-felonstonewlyreleased felons(Apaorg,2022)

Successfulrehabilitationprogramshavebeenshownto increasethechancesofsuccessfulrehabilitationand reducethelikelihoodofrepeatedcriminal behavioralongwithtacklingthementaltrauma,that leadsthemtobecomestablementallyandsocially.

1.

Hypothesis

Convictedfelonswouldhavereduced criminalactivitiesandbetter psychologicalbehaviorsafter incarceration.

Discussion

Thisstudydemonstratedhowprisoners'psychological behaviorsalteredoncetheywerereleasedfromjail, showinghowbeingimprisonedchangedtheirconductin theoutsideworld.

Thefindingsshowadownwardshiftinthe behaviorsofconvictedfelonsfrombeforeandafter imprisonment. Manyconvictedfelonshave deterioratedmentalhealthafterbeingseparated fromfamilymembersforlongperiodsoftime (Quandt&Jones,2021).

TheWorldHealthOrganizationclaimsthatviolent conditions,alackofsocialinteraction,playarole inthedeclineofoffenderswhoarereleased,causing themtorelapseintothehabitratherthanimprove (Quandt&Jones,2021).

Potentiallimitationstothisexperimentinclude sampleorself-reportingbias,astheresultsmay notencompasstheresultsofallprisoners.

References

Apaorg (2022) Availableat: https://www.apa.org/monitor/2022/10/lifeafter-prison.

Graves,S.(2020).ManyCaliforniansinPrisons andJailsHaveMentalHealthNeeds.[online] CaliforniaBudget&PolicyCenter.Availableat: https://calbudgetcenter.org/resources/prisonsand-jails-have-mental-health-needs/.

Petersilia,J.(2011)'Beyondtheprisonbubble', TheWilsonQuarterly,35(1),50+,available: https://link.gale.com/apps/doc/A275575034/AO NE?u=nysl me midhsl&sid=bookmarkAONE&xid=97b9204b[accessed10August 2023].

Quandt,K.R.andJones,A.(2021)Research roundup:Incarcerationcancauselasting damagetomentalhealth,PrisonPolicy Initiative.Availableat: https://www.prisonpolicy.org/blog/2021/05/13/ mentalhealthimpacts/(Accessed:14August 2023)

Acknowledgments

AreebahLashirah,ZohieBetts,RishaRao,AyushSinha