HSS GENE EDITING HOW CRISPR/CAS9 TECHNOLOGY HAS REVOLUTIONIZED DISEASE TREATMENT

RAYAN SHUJA

Recent headlines speak of the strides that have been made within gene therapy and how we are within a few years of mass adoption. While the scientific community has been steadily progressing towards treating gene related diseases and ailments, gene editing itself remains largely esoteric. Most people know as much about DNA as they learned in their high school biology classes and often feel too confused by the large body of scientific literature to pursue the matter in further depth.

The history of gene manipulation starts in 1953 when the work of Rosalind Franklin, a researcher at Birkbeck College in London, led to the discovery of DNA’s double helix structure (Synthego). By understanding the nature of DNA as having two different strands that wound around each other, the door was opened for other researchers to make further advancements in the field of genetics.

Two milestone events caused an explosion within the field of gene editing. The first was the cloning of Dolly the sheep, which both brought the field of genetic experimentation in the public eye and confirmed the ability of adult cells to be substantially altered. The second milestone, while not as widely talked about, is often referred to as ‘one of the greatest scientific feats in history’ – the Human Genome Project (Synthego). The project was an international effort to study and catalog the entire set of DNA of different organisms. In April 2003 it made headlines by constructing the first sequence of the human genome and providing scientists with fundamental information about what makes humans function (NHGRI). The completion of the Human Genome Project had a wild cascade effect within all fields of biology and chemistry, and paved the way for mass gene therapy and enhancing our ability to treat diseases from herpes to cancer (ASGCT).

Early on many scientists were quick to point out the profound ethical implications of altering the genetic code. In 1975 the Asilomar Conference on Recombinant DNA was convened to help draft ethics guidelines concerning biotechnology, the effects of which are still felt in the industry today (Synthego).

In 2012 the key mechanisms behind CRISPR were discovered by Jennifer Doudna, Emmanuelle Charpentier associated with the Max Planck Unit for the Science of Pathogens and the University of California, Berkeley, and quickly became a functional mechanism for widespread gene editing (Science). CRISPR-Cas9 (often referred to as CRISPR) is a naturally occurring system in bacterial defense systems which chops up the DNA of would-be virus invaders. It does this through the Cas9 enzyme, which is able to act like a molecular scissor and precisely cut DNA in known locations

Through further research, scientists have developed methods that allow them to use these ‘scissors’ to cut DNA, and insert new pieces of DNA, and ‘glue’ the strands back together (Your Genome).

The first published use of CRISPR on human cells came in 2015 when Junjiu Huang of Sun Yat-Sen University in Guangzhou tried to remove a gene responsible for a blood disease from embryos (Regalado 2020). While they did not mature into fetuses, it marked the shift from “designer babies” - a baby whose genes have been selected for a potentially altered - being a farcical dream to a legitimate possibility. A possibility which came true a mere three years later in late 2018 when He Jiankui, an associate professor at the Southern University of Science and Technology in Shenzhen, claimed to have created the first genetically modified babies (Cryranoski 2019). He removed a particular gene from the genetic code of a pair of twins in an attempt to prevent them from contracting the fathers’ HIV. While preliminary evidence supported the success of his operation, he was immediately lambasted by the entirety of the international community for flouting ethics guidelines and failing to properly ensure no unintended harm would come to the children - potentially unintentionally altering other parts of the genome . There were calls for an international moratorium on fetal genetic editing and the Chinese government put Jiankui in jail for 3 years. While the moratorium was never created it is still frowned upon by the scientific community to perform any genetic editing of germ-line cells (Wolinetz & Collins 2019).

As a result, there came a greater focus on therapeutic gene editing for adults to potentially treat diseases such as Sickle-Cell Anemia and Muscular Dystrophy. Since the first approved human trials in 2018, we have now reached the point where earlier this year, in November, the CDC approved the first gene therapy to treat Hemophilia B (Ramesh 2022).

From the discovery of DNA all the way until the first available genetic therapy, humanity is on the verge of being able to remodel itself however it desires. From the treatment of genetic diseases of all varieties to the creation of designer babies, this is a turning point in our medical technology. Regardless of the degree to which neonatal editing is done, it will be one of the most pertinent moral dilemmas of the next generation - while we can’t predict the future, it looks like genetic editing will be integrated in one way or another.

References

Synthego (n.d.). History of Genetic Engineering and the Rise of Genome Editing Tools. Retrieved January 13, 2023, from https://www.synthego. com/learn/genome-engineering-history

National Human Genome Research Institute (n.d.). The Human Genome Project. Retrieved January 13, 2023, from https://www.genome.gov/ human-genome-project

ASGCT. (n.d.). Gene therapy basics. Retrieved January 13, 2023, from https://patienteducation.asgct.org/gene-therapy-101/gene-therapybasics

Science. (n.d.). CRISPR, the revolutionary genetic ‘scissors,’ honored by chemistry Nobel. Retrieved January 13, 2023, from https://www. science.org/content/article/crispr-revolutionary-genetic-scissors-honoredchemistry-nobel

Your genome. (2022, February 8). What is CRISPR-Cas9?. Retrieved January 13, 2023, from https://www.yourgenome.org/facts/what-iscrispr-cas9/

Regalado, A. (2020, April 2). Years before CRISPR babies, this man was the first to edit human embryos. MIT Technology Review. Retrieved January 13, 2023, from https://www.technologyreview. com/2018/12/11/138290/years-before-crispr-babies-this-man-was-thefirst-to-edit-human-embryos/

Cyranoski, D. (2019, February 26). The CRISPR-baby scandal: What’s next for human gene-editing. Nature News. Retrieved January 13, 2023, from https://www.nature.com/articles/d41586-019-00673-1

Wolinetz, C. D., & Collins, F. S. (2019, March). NIH supports call for moratorium on clinical uses of germline gene editing. Nature. Retrieved January 13, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC6688589/

Ramesh, S. (2022, November 26). New US-approved gene therapy for haemophilia B world’s most expensive drug - $3.5 mn per dose. ThePrint. Retrieved January 13, 2023, from https://theprint.in/health/new-usapproved-gene-therapy-for-haemophilia-b-worlds-most-expensive-drug3-5-mn-per-dose/1236938/