- A high throughput screen of >30,000 diverse repressor domains from across the tree of life identifies repressor domains with unique structures that underpin enhanced epigenetic effector domain potency.
- These repressor domains have been utilized to enhance Scribe's Epigenetic Long-Term X-Repressors (ELXRs), making them more potent than current Cas9-based repressors.
- ELXR offers a promising epigenetic editing approach to treat dyslipidemias with best-in-class efficacy at lower therapeutic doses.
ALAMEDA, Calif.--(BUSINESS WIRE)--#ALS--Scribe Therapeutics Inc. (Scribe), a genetic medicines company unlocking the potential of CRISPR to transform human health, presented data on its Epigenetic Long-Term X-Repressor (ELXR) technology at the 2025 Keystone Symposia on “Precision Genome Engineering: Translating the Human Genome to the Clinic” conference. The Symposia Spotlight presentation showcases Scribe’s CRISPR by DesignTM approach to engineering potent ELXRs with newly uncovered repressor domains and their validation in animal models, including non-human primates. Notably, a single dose of ELXR using a newly identified repressor domain achieved ~90% repression of PCSK9—a key driver of dyslipidemia—lasting at least 150 days in non-human primates. The identification and use of a newly discovered repressor domain enables the creation of more effective epigenetic editors with a broader therapeutic window than current Cas9-based repressors.
“Scribe is redefining what’s possible with CRISPR technology. Our latest data showcase the unmatched potency of our novel epigenetic editors, bringing safer, more effective therapies to patients with dyslipidemias and other cardiometabolic diseases,” said Benjamin Oakes, Ph.D., co-founder and Chief Executive Officer of Scribe. “We believe this is more than an advancement—it’s a leap toward rewriting the future of medicine.”
Highlights from the oral presentation include:
- Scribe engineered novel, potent epigenetic editors (ELXRs) using newly identified repressor domains to durably and effectively silence gene expression without altering the genome
- These newly discovered, compact repressor domains were identified through high-throughput screening of over 30,000 diverse domains across the tree of life
- Structural, functional, and sequence analyses provided novel insights into understanding how to optimize potency of epigenetic editors
- Newly identified repressor domains significantly enhance ELXR activity in vitro and in vivo studies, including in non-human primates, outperforming the standard domain used in current Cas9-based repressors
- Data highlight the potential of engineering to create more effective epigenetic editors that can be delivered at lower therapeutic doses, enabling therapeutic gene silencing with improved potency and safety
About Scribe Therapeutics
Scribe Therapeutics is revolutionizing medicine by developing optimized in vivo CRISPR-based genetic medicines designed to become standard of care treatments for patients suffering from highly prevalent diseases, starting with cardiometabolic disease. The company is on a mission to build the first CRISPR-based therapeutics that are effective and safe enough to transform everyone’s lifetime risk for disease. Scribe’s CRISPR by Design™ approach engineers bacterial immune systems into a premier suite of genome and epigenome editing tools built for unique molecular advantages in activity, specificity, and deliverability, enabling the creation of therapies with a broader therapeutic window and safe for use as a preventative treatment. The company’s lead candidate, STX-1150, is a novel liver-targeted therapy designed to epigenetically silence the PCSK9 gene, resulting in significant and durable reduction of LDL-C levels. To broaden and accelerate the impact of its engineered CRISPR technologies for patients, Scribe has formed strategic collaborations with world-leading pharmaceutical companies including Sanofi and Eli Lilly. Co-founded by Nobel Prize winner Jennifer Doudna and backed by leading life sciences investors, Scribe is engineering the future of genetic medicine. To learn more, visit www.scribetx.com.
Contacts
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Thermal for Scribe Therapeutics
