Scribe Therapeutics Presents Epigenetic X-Repressor Data at 2025 Keystone Symposium
Scribe Therapeutics Inc. (Scribe), a leading genetic medicines company leveraging the power of CRISPR technology to transform human health, recently presented groundbreaking 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. During the Symposia Spotlight presentation, Scribe unveiled the potential of its CRISPR by Design™ approach, which enables the engineering of highly potent ELXRs using newly identified repressor domains. These domains have been validated through various studies, including animal models and non-human primates, demonstrating remarkable effectiveness in gene silencing.
A standout result from the presentation revealed that a single dose of ELXR, utilizing a newly discovered repressor domain, achieved approximately 90% repression of the PCSK9 gene, a key contributor to dyslipidemia. Notably, this repression persisted for at least 150 days in non-human primates. This breakthrough underscores the power of Scribe’s innovative technology in creating more effective epigenetic editors, offering a broader therapeutic window compared to traditional Cas9-based repressors.
“Scribe is redefining the capabilities of CRISPR technology,” said Benjamin Oakes, Ph.D., co-founder and Chief Executive Officer of Scribe. “The data we presented not only highlight the unmatched potency of our novel epigenetic editors but also demonstrate the potential to develop safer, more effective therapies for patients suffering from dyslipidemias and other cardiometabolic diseases. This is more than just an advancement; it is a leap toward rewriting the future of medicine.”
Key Highlights from the Presentation
The oral presentation at the Keystone Symposia outlined several key advancements in Scribe’s work:
- Engineering Potent Epigenetic Editors: Scribe’s team developed novel, potent epigenetic editors (ELXRs) that use newly identified repressor domains. These editors can silence gene expression in a durable and effective manner without altering the genome itself.
- Identification of New Repressor Domains: Through high-throughput screening of over 30,000 diverse repressor domains sourced across the tree of life, Scribe identified compact repressor domains that significantly enhance the potency of ELXRs. This discovery marks a significant advancement in the precision of epigenetic editing.
- Optimizing Potency: By conducting detailed structural, functional, and sequence analyses, Scribe gained new insights into optimizing the potency of its epigenetic editors. This allowed them to achieve more effective gene silencing both in vitro and in vivo.
- Superior In Vivo Performance: The newly identified repressor domains demonstrated significantly enhanced ELXR activity in non-human primates, outperforming the standard domains used in current Cas9-based repressors. These results suggest the potential for more efficient epigenetic editing, requiring lower therapeutic doses for effective gene silencing.
- Improved Safety and Potency: The advancements in ELXR technology also pave the way for therapies that can be delivered at lower doses, providing enhanced potency and safety for patients. This could be a game-changer for therapeutic gene silencing, offering a safer alternative with improved long-term efficacy.
Scribe’s Mission and Impact
Scribe Therapeutics is revolutionizing the field of medicine by developing optimized in vivo CRISPR-based genetic medicines with a focus on addressing highly prevalent diseases, beginning with cardiometabolic conditions. The company’s mission is to create the first generation of CRISPR-based therapeutics that are not only effective but safe enough to transform the long-term risk for diseases in everyone. Scribe’s innovative CRISPR by Design™ approach leverages engineered bacterial immune systems to provide unique molecular advantages in activity, specificity, and deliverability. This platform enables the creation of therapies that have a broader therapeutic window, ensuring safety for use as preventative treatments.
One of the company’s most promising candidates is STX-1150, a liver-targeted therapy designed to epigenetically silence the PCSK9 gene. This results in a substantial and durable reduction in LDL cholesterol (LDL-C) levels, a critical factor in managing cardiovascular risk. STX-1150 has the potential to offer significant improvements in the treatment of dyslipidemia, particularly for patients who do not respond well to traditional therapies.
About Scribe Therapeutics
Scribe Therapeutics is dedicated to revolutionizing medicine by developing in vivo CRISPR-based therapies designed to treat and prevent diseases with high prevalence, starting with cardiometabolic diseases. The company’s CRISPR by Design™ approach utilizes engineered bacterial immune systems to create a suite of genome and epigenome editing tools. Scribe’s lead candidate, STX-1150, aims to provide a durable reduction of LDL-C levels, offering a new frontier in dyslipidemia treatment. Through strategic partnerships and its innovative platform, Scribe is poised to transform the future of healthcare.
