SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Epic Bio, a leading epigenome engineering company developing therapies to modulate gene expression using ultracompact, non-cutting dCas proteins, has presented new data demonstrating the achievement of persistent gene activation using its Gene Expression Modulation System (GEMS) platform. The data were presented at the Keystone Symposia’s Chromatin Architecture in Development and Human Health conference, taking place March 12-15, 2023, in British Columbia, Canada.
“These data are a thrilling proof-of-principle for our GEMS platform’s ability to generate new therapeutic constructs that can overcome longstanding challenges within genetic medicine. In this case those challenges were two-fold: no one has yet demonstrated epigenetic gene activators with more than a short-lived effect, and secondly, even those short-lived activators are too large to be packaged within a clinically validated AAV vector, limiting their use as in vivo therapies,” said Dan Hart, Ph.D., head of technology development at Epic Bio. “Here we’ve documented discovery of novel activators that successfully overcome those challenges, producing durable activation that is passed down through cell divisions after just a single, transient exposure to our GEMS construct.”
The novel activators were discovered through the use of a proprietary cell-based reporter platform, and then optimized for greater potency and smaller size using machine learning algorithms through successive rounds of protein engineering and evaluation in cellular models. The activators, when fused to a dCas and targeted to native gene promoters, were observed to have a greater magnitude and duration of effect (up to 80 cell divisions) compared to standard multi-protein domain fusions such as VPR, which is only durable for a dozen cell divisions. Furthermore, the coding length of the entire construct was just 1/10th that of comparator approaches, allowing it to fit within a single AAV vector.
“This study highlights all the powerful differentiators built into our GEMS platform: non-cutting, precisely targeted modulation of gene expression produced by a smaller payload than has ever before been possible,” said Amber Salzman, Ph.D., chief executive officer of Epic Bio. “The kind of persistent activation we’ve shown here could be transformative for the treatment of haploinsufficient diseases, by offering a way to durably restore gene expression to normal physiological levels. As we continue to advance our first GEMS candidate toward clinical readiness, we are excited to build upon these findings and to rapidly work to translate them into meaningful therapies for people with previously intractable diseases.”
A PDF of the poster may be accessed under the Science section of Epic Bio’s website.
About Epic Bio
Epic Bio is a leading epigenome engineering company, leveraging the power of CRISPR without cutting DNA. The company is using its proprietary Gene Expression Modulation System (GEMS) to develop therapies. Through the company’s library of the most compact Cas DNA-binding proteins to work on human cells, the company is developing in vivo therapies with delivery via a single AAV vector. Epic Bio has an initial focus on Facioscapulohumeral Muscular Dystrophy (FSHD) and is conducting additional research to address Antitrypsin Deficiency (A1AD), Heterozygous Familial Hypocholesterolemia (HeFH), as well as other indications. The company is financially backed by Horizons Ventures and other leading investors. Visit www.epic-bio.com for more information or follow us on Twitter and LinkedIn.
