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Biomedical science is supporting advancements in gene editing technologies

University of Gloucestershire lecturer Dr Robbie Baldock has highlighted challenges to advancements in gene editing technologies that could put an end to serious diseases.

Dr Baldock, a Senior Lecturer in Biomedical Sciences within the University’s School of Natural and Social Sciences, aims to uncover the mechanisms of DNA repair used in maintaining genomic stability, which is crucial for the health and development of humans and animals.

The power of gene-editing technologies has already enabled the destruction of simian immunodeficiency virus DNA from infected rhesus macaque monkeys and is helping to control mosquito populations to supress the spread of malaria.

But while gene editing tools used in medicine and biological sciences have the potential to help prevent genetic diseases, any unwanted DNA repairs or edits can lead to disease, including cancer.

Dr Baldock said: “Novelists and screenwriters have bombarded our imaginations with the idea of genetic engineering.

“From superhero origin stories to theme parks inhabited by dinosaurs, the prospect of re-writing the genetic code has inspired many and raised many ethical questions.

“The potential for these tools in medicine and biological sciences to prevent genetic diseases is readily being explored. 

“New gene-editing tools have made genome editing faster, more accurate and cheaper than ever before, but with so much at stake we need to carry out more research to ensure they work safely and that the desired edits will be made.”

There are several tools that enable scientists a way of altering the genome, including zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs) and the more recent CRISPR, or clustered regularly interspaced short palindromic repeat.

These tools damage DNA at a targeted location and can be programmed to create double-strand breaks (DSBs), also known as chromosome breaks, at a defined location within the genome.

The DSB needs to be repaired for normal development of the cell, otherwise mutations can lead to genomic instability, which can cause cancer and other diseases.

Dr Baldock explained: “Gene editing technologies have the potential to treat or even cure genetic diseases, but any edits need to be made consistently and accurately to ensure only the required genetic changes are introduced.

“This relies on multiple cellular processes that are collectively referred to as DNA repair mechanisms.

“Our research so far has helped understand which genetic variants in DNA repair coding genes block specific mechanisms of repair.

“Alongside influencing cancer susceptibility, these variants may influence the types of edits that will likely be produced from the repair of DSBs and will likely have implications for future clinical applications.

“Understanding DNA repair mechanisms in further detail will be vital to improve gene editing technologies further, so that only intended genetic edits are made.”

In his latest peer-reviewed paper, Beyond base excision repair: an evolving picture of mitochondrial DNA repairpublished in Bioscience Reports, Dr Baldock examined the way in which mitochondrial DNA damage can be repaired.

Through studying published data and previous research, Dr Baldock hopes that by understanding the mechanisms that help protect mitochondrial DNA, it may explain why some patients suffer adverse drug reactions.