Data demonstrate proprietary X-Editors engineered using Scribe’s CRISPR by Design™ approach are a promising gene editing platform for developing genetic medicines with high activity, specificity and deliverability

Scribe Therapeutics Inc., a genetic medicines company unlocking the potential of CRISPR to transform human health, will present data on its X-Editing (XE) technologies today at the 26th American Society of Gene and Cell Therapy (ASGCT) Annual Meeting being held in Los Angeles, Calif. and virtually. The data validate the company’s CRISPR by Design™ approach as well as its XE technology as a potent and flexible platform for gene editing.

“Molecular engineering is the foundation of Scribe’s philosophy. We are pleased to present data on our proprietary gene editing technology, the ‘X-Editor’ — a highly evolved version of CasX that is proven to perform at efficiency levels orders of magnitude higher than many naturally occurring CRISPR molecules,” said Benjamin Oakes, Ph.D., Chief Executive Officer of Scribe. “The data we are presenting showcase the power of our engineering engines to drive the creation of unique and highly effective genome modification technologies.”

Scribe’s CRISPR by Design™ approaches enabled the company to hone natural CRISPR enzymes into technologies that exhibit the molecular advantages of high genome editing activity, specificity and deliverability necessary to develop best-in-class ex vivo and in vivo therapeutics. The data presented at ASGCT demonstrate that holistically engineering CRISPR-based therapies is critical for achieving the therapeutic profile necessary for safe and effective genetic medicines.

Highlights from the oral presentation include:

• Scribe generates screening systems and libraries consisting of tens of thousands of CasX variants to comprehensively map the fitness landscape for this enzyme, allowing for identification of beneficial classes of mutations
• Iterative selections across the sequence landscape combined with structural, biochemical and functional analyses give Scribe the unique ability to selectively optimize its enzymes along multiple axes, including specificity and activity
• Engineering of the CasX guide RNA through comprehensive mutagenesis provides an additional dimension of optimization, resulting in orders of magnitude of improvement
• Scribe’s advanced X-Editor, which is more than 125 steps in sequence space removed from naturally occuring CasX, outperforms other small and engineered Cas enzymes including SaCas9, Cas9 variant sRGN, Cas12f variants, Casɸ and wild-type CasX
• In primary human immune cells, X-Editors demonstrated greater than 90% editing rates for knock-out of a single gene target, comparable to SpyCas9, and XE delivered in vivo achieved robust gene editing in every organ system tested including the eye, brain, muscle and liver

Oral presentation details:

Title: Comprehensive Engineering of CasX Holoenzyme to Create an X-Editor with High Activity, Specificity and Deliverability

Abstract Number: 262

Session Title: Genome & Epigenome Editing Technologies I

Date: Friday, May 19, 2023

Time: 5:15 - 5:30 p.m. PT

Location: Concourse Hall 152 & 153, Los Angeles Convention Center, Los Angeles, CA

Speaker: Addison Wright, Ph.D., Principal Scientist at Scribe

About Scribe Therapeutics

Scribe Therapeutics is revolutionizing the development of optimized genetic medicines that have the potential to durably treat disease at scale. Our CRISPR by Design™ approach engineers bacterial immune systems into a premier suite of genome editing tools built for unique molecular advantages in activity, specificity and deliverability that translate into safer and more effective genetic therapies. 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.

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We are pleased to present data on our proprietary gene editing technology, the ‘X-Editor’ — a highly evolved version of CasX that is proven to perform at efficiency levels orders of magnitude higher than many naturally occurring CRISPR molecules.