Precision BioSciences Announces Publication in Nucleic Acids Research Elucidating the Mechanisms for High Efficiency Gene Insertion in Dividing and Non-Dividing Cells Using ARCUS Nucleases

Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for high unmet need diseases, today announced the publication of a peer-reviewed manuscript titled “High-Efficiency Homology-Directed Insertion into the Genome using the Engineered Homing Endonuclease ARCUS” in the journal Nucleic Acids Research. This publication demonstrates a wide variety of gene edits including high-frequency transgene insertions using ARCUS nucleases to stimulate a homology dependent repair mechanism. The publication provides evidence to understand the repair mechanism and how ARCUS can produce high insertion frequencies in both dividing and non-dividing cells.

“We are pleased to have been published in Nucleic Acids Research and to be able to highlight many of the key areas where ARCUS is able to differentiate itself as a premier genomic editing platform. ARCUS continues to demonstrate capabilities beyond what is possible with other current genome editing technologies,” said Jeff Smith, Ph.D., Co-Founder and Chief Research Officer at Precision BioSciences. “With ARCUS, we’re able to unlock the full spectrum of DNA editing approaches, from precise single base changes and small targeted deletions to more complex insertions, even replacing large segments of genomic DNA with efficiencies of 60-90% in dividing cells and 20-40% in non-dividing cells. The small size of ARCUS and its broad capabilities present advantages for application in a diverse range of diseases including those we are validating in ongoing clinical trials.”

Highlights from the publication include:

• ARCUS nucleases support rates of transgene insertion exceeding 85% in T lymphocytes via homology-directed repair (HDR).
• Through its unique ability to generate 3’ overhang ends at the DNA break, ARCUS can facilitate transgene insertion in up to 40% of non-dividing primary human hepatocytes.
• ARCUS editing by HDR can also be used to achieve other gene editing objectives such as gene insertion, single base editing, specific small and large deletions, and replacement of large stretches of genomic DNA which could enable editing of genes that are too large for gene therapy approaches.
• Mechanistic studies demonstrate the necessity of the 3’ overhang that ARCUS nucleases create to drive homology-mediated gene insertion in dividing and non-dividing cells.

“Our pipeline of wholly owned and partnered in vivo gene editing programs demonstrate the broad applicability of ARCUS, leveraging the unique properties for gene insertion (e.g. ECUR-506), gene elimination (e.g. PBGENE-HBV), and excision of large sequences of DNA (e.g. PBGENE-DMD) to address the broadest variety of diseases. We’re excited about the continued progress with our ARCUS platform and the opportunity to durably improve the lives of people with genetic and infectious diseases,” said Cassie Gorsuch, Ph.D., Chief Scientific Officer at Precision BioSciences.