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Advances in gene modification could lead to disease-resilient livestock Scientists at the Roslin Institute feel they are on the fast track to producing genetically modified pigs resistant to African swine fever. Genome editing allows scientists to make precise modifications to an organism’s genetic makeup. These genome editors are commonly known as ‘molecular scissors’ because they can be used to cut parts of DNA. There are three types of genome editors: Transcription activator-like effector nuclease (TALEN), Zinc Finger Nuclease (ZFN), and the most recent and currently being discussed in the media, CRISPR-Cas9. In 2013, researchers at the Roslin Institute used both TALENs and ZFN with a pig zygote, or a fertilized egg, to compare the results, and were able to produce live genome-edited pigs. Pig

26 showed that gene editors were able to precisely edit the genome of a pig zygote by removing exactly one DNA base without any trace of alteration to the rest of the vast genome of the pig. This was a valuable advancement in producing viable livestock resilient to disease. Nearly three years after Pig 26, Roslin scientists have progressed one step further. Spread by ticks, African swine fever is highly contagious and fatal to farmed pigs. However, the pig’s wild cousin, the warthog, is resistant to the disease, thanks to its genetic makeup. Roslin scientists altered the genetic code of the farmed pigs by editing five letters of a gene, making it the same to that of the warthog. They believe the genetic modification is able to produce pigs possibly resistant to the African swine fever virus. Although the disease has never been found in the UK, outbreaks are rampant in Russia and Sub-Saharan Africa, causing concern among farmers that the disease could spread. Controlled trials are currently underway at the Roslin Institute to test whether the genetically modified pigs are indeed resistant to the disease. Lynda-Marie Taurasi

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Personalising ovarian cancer treatment Why do some patients respond well to treatment while others don’t? Why do some cancers shrink away when exposed to therapy, while others grow on regardless? In ovarian cancer, a disease which claims the lives of around 150,000 women per year worldwide, differences in survival and response to therapies are particularly striking. Some patients respond well to treatment, while others quickly succumb to their disease. Researchers in the Ovarian Cancer Translational Research Group at the Edinburgh Cancer Research Centre are working to try and uncover the reasons behind these differences between patients. The idea is to look back at previous patients and examine their disease at the molecular level. This can involve looking at exactly how certain genes are encoded by sequencing their DNA, or by looking at how the genes are being used in the tumour. Then we compare what we find to which treatments

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worked well for a patient to see if we can find groups of people that respond well to certain therapies. Once we’ve found these associations, new patients can be tested to see which of these groups they fit into. In this way, their therapy can be tailored to the biology of their disease—an idea commonly known as personalised medicine. Understanding the biology behind ovarian cancers also helps us identify new ways to target cancer cells, while leaving normal cells unharmed. These new treatment options might be drugs that are already being used in other diseases or cancer types, or they might be completely novel. Targeted therapies can be very effective, but most tumours eventually become resistant to these agents. Understanding how this resistance develops is important for finding ways of re-sensitising disease to therapy, and for choosing new treatment strategies once a particular drug has stopped working. Looking at patients who respond exceptionally well or who don’t respond at all is particularly key to understanding this. Together, these research avenues point us toward new drugs for the treatment of ovarian cancer. They help us identify the patients that are likely to benefit most from new therapies, have the highest chance of success on conventional chemotherapy and those who may benefit from different ways of administering treatment. The key is to rapidly translate what we find in the laboratory back into clinical practice to improve the treatment and management of patients diagnosed with ovarian cancer.

Robb Hollis

EUSci #19  

Issue 19 of the Edinburgh University Science Magazine

EUSci #19  

Issue 19 of the Edinburgh University Science Magazine