Target validation is a crucial step in pre-clinical drug discovery workflows that builds confidence on the identification of a genetic target as relevant to a disease. With recent advancements, CRISPR serves as a particularly powerful tool for this process, as it enables researchers to accurately modify genes and determine their function in a variety of experimental systems.

One scientist leveraging CRISPR gene editing in this way is Dr. Panos Zalmas, Head of the Open Targets Validation Lab based at the Wellcome Sanger Institute, whose work focuses on discovering and validating new putative disease targets for the development of safe and effective medicines.

In this SelectScience^® interview, we speak with Zalmas to learn how he is working to improve the rate of target adoption into drug discovery pipelines across therapy areas such as oncology, neurodegeneration, and immunology and inflammation. Here, Zalmas explains the importance of gene editing in his target validation workflows and highlights how CRISPR technologies in particular are key to the success of drug discovery.

Researchers have been able to reduce dramatically the level of bad cholesterol in human subjects after injecting them with an experimental gene editing treatment, according to the science journal Nature, which is the first time this technique, called base editing, has been done on humans.

But at least one person died after receiving an infusion, prompting a round of safety concerns.

In the clinical trial, 10 subjects with congenitally high levels of bad cholesterol, aka low-density lipoprotein (LDL), were given an injection of VERVE-101, a gene-editing treatment that uses the base editing technique. This treatment then turned off the gene for the protein PCSK9, which is found in the liver and regulates LDL. High levels of LDL can lead to coronary heart disease.