Daniel Hart, PhD, on CRISPR-Mediated In Vivo Epigenomic Activation

“We've become interested in this other side of epigenetic regulation, which is that you can turn genes on. So, I think people are familiar with the idea you can turn genes off with epigenetic editing but switching them on is something that has not really been demonstrated before. So, we set up screens to identify these factors, [were] successful in doing so. Now that we have them, I think the challenge is understanding what the best applications would be for them, but I think it's easy to imagine deploying them in diseases known as haploinsufficiencies.”

CRISPR-mediated novel epigenetic activators demonstrated durable gene activation in both immortalized and primary cells, with 2-fold activation of LDLR sustained for up to 5 weeks in primary human hepatocytes within a humanized mouse liver model. LDLR haploinsufficiency constitutes 85 to 90% of genetically confirmed cases of familial hypercholesterolemia and these data validate the potential of epigenetic activation of disease-modifying genes in vivo.

Daniel Hart, PhD, Senior Director and Head of Technology Development, Epic Bio, presented these data at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland. CGTLive spoke with Hart to learn more about the findings and their significance in the field. He shared further research that Epic is conducting with epigenomic activation and potential applications of the technology in the future. He also shared his excitement for the growing prominence of epigenomic editing and nonviral strategies for gene editing.

REFERENCE

Carosso G, Yeo R, Gainous TB, et al. Compact Epigenetic Modulators for CRISPR Mediated Persistent Gene Activation. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #56