IGI Seminar Series: Writing DNA with RNA: Genome Engineering by Target-Primed Reverse Transcription

Summary

The ability to introduce new DNA sequence into the genome with high specificity and efficiency would provide a critical complement to existing gene editing approaches. We are developing RNA Gene WritersTM, which are unique and engineerable gene editing constructs that use all-RNA components and harness the mechanism of target-primed reverse transcription, or TPRT, to introduce a broad range of alterations to the genome, from inserting a transgene or exon to introducing single nucleotide changes. Gene Writers are designed to provide an attractive toolkit for the treatment of a wide variety of genetic or common diseases. Here we will discuss our approach to screen for and engineer RNA Gene Writers that enable a full spectrum of edits when delivered as all-RNA components to primary cells in vitro and in vivo. In addition, we will present on the application of our Gene Writers when delivered to hepatic and extra-hepatic tissues for the correction of single nucleotide mutations known to be responsible for monogenic diseases, as well as, for the insertion of full-length genes to generate CAR-T cells in vitro and in vivo. Taken together, we demonstrate that our RNA Gene Writers are highly versatile and have the potential to be applied in vivo for a wide range of therapeutic applications.

Speaker

Dr. Michael Holmes joined Tessera in December 2021 as Chief Scientific Officer. Dr. Holmes has over 20 years of experience working on the development and clinical translation of different genome editing- and gene therapy-based strategies for the treatment of inherited and acquired diseases. He has a proven track record of translating genomic engineering technologies to product candidates as evidenced by leading ten therapeutic programs across a landscape of ex vivo and in vivo therapies.

Prior to joining Tessera, Dr. Holmes served as the Chief Scientific Officer with Ambys Medicines, where he led the research and development efforts in the identification, creation, and advancement of novel therapies for severe liver diseases. Previously, Dr. Holmes worked for 17 years at Sangamo Therapeutics, Inc. rising through the ranks to Senior Vice President and Chief Technology Officer. During this time, he was heavily involved in the company’s research and pipeline development of genetic  therapies.

Dr. Holmes has authored over 60 publications in the field of genome editing and gene regulation and is listed as an inventor of over 40 issued and pending U.S. patents related to genome editing and targeted gene regulation technologies. He holds his Ph.D. in Molecular and Cell Biology from the University of California, Berkeley (working in Robert Tjian’s lab) after earning his B.S. in Molecular Biology from the University of California, San Diego.