Chroma Medicine highlighted data demonstrating the advantages of epigenetic editing for multiplex gene regulation at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting in Los Angeles. The presentation entitled “Multiplexed Editing Without Chromosomal Rearrangements Using Epigenetic Editors” was given by Sahar Abubucker, senior director, data science.
Chroma’s epigenetic editing platform harnesses the cell’s endogenous mechanism for regulating gene expression to durably modulate transcription without cutting or nicking the DNA, offering a potentially safer approach for multiplex editing according to company officials. They add that this avoids challenges associated with gene editing methods that rely upon DNA breaks to alter gene expression. These techniques have the potential to induce unnecessary risks, including chromosomal rearrangements when multiplex editing several genes simultaneously, maintains Vic Myer, PhD, Chroma’s president and CSO.
Key advantages of epigenetic editing
The data presented at ASGCT demonstrate the key advantages of epigenetic editing for multiplex gene regulation compared to Cas9-based approaches, continued Myer. Application of Chroma’s epigenetic editor to three different genes simultaneously accomplished durable silencing in primary human T cells.
Sequencing and single-cell imaging assays indicated that multiplex epigenetic editing did not induce indels, chromosomal rearrangements, or other unintended genomic alterations compared to controls. Conversely, cells simultaneously edited using a Cas9 nuclease exhibited a significant number of translocations and other inadvertent breaches to genomic integrity, pointed out Myer.
“These results underscore one of the key advantages of harnessing nature’s innate mechanism for precise gene regulation. By modulating expression without cutting DNA, we can safely and efficiently target multiple genes simultaneously,” he explained. “Taken together [with other] results [that demonstrated] durable and highly efficient silencing of PCSK9 and hepatitis B virus, these data validate our platform and its distinct advantages, positioning us to advance a broader pipeline of epigenetic editing therapeutics.”
“Data presented at ASGCT by Chroma and our scientific founders represent an important step toward rapidly advancing these medicines to patients,” said Catherine Stehman-Breen, MD, Chroma’s CEO. “We are committed to rigorously progressing our pioneering epigenetic editing technology and programs and are pleased to present data supporting the therapeutic promise of epigenetic editing for gene regulation while preserving genomic integrity.”