On December 8, 2021 Metagenomi, a genetic medicines company with a versatile portfolio of next-generation gene editing tools, reported that the company will share data related to their novel, compact, and hypo-immune gene editing systems at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), which is taking place in Atlanta, GA and virtually, December 11–14 (Press release, Metagenomi, DEC 8, 2021, View Source [SID1234596619]).

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"The development of CAR T therapies and other genetically engineered cell therapies in recent years has resulted in significant benefits for patients, yet there remains a large unmet need for gene editing systems that can be used to develop novel immunotherapy approaches to treat blood cancers," said Brian C. Thomas, PhD, CEO and Co-Founder of Metagenomi. "At ASH (Free ASH Whitepaper), we are presenting data on our novel nucleases that display highly efficient and specific gene editing both in vivo and ex vivo and hold significant potential to drive the development of new and efficacious therapies for patients."

In a poster titled "A Novel Type V CRISPR System with Potential for Genome Editing in the Liver," it is shown that Metagenomi’s novel Type V CRISPR-associated nuclease was highly active in the liver of mice when systemically administered via lipid nanoparticles (LNP). The nuclease was derived from a unique natural environment and is phylogenetically distinct from previously identified Type V systems. Moreover, no antibodies to the nuclease were detected in serum from 50 healthy human donors, while between one third and half of the same serum samples contained antibodies that bind to spCas9, which is derived from a Streptococcus bacteria that commonly infects humans. In summary, this novel Type V CRISPR-associated nuclease is a promising new gene editing system for in vivo editing of the liver.

In a separate poster titled "Novel CRISPR-Associated Gene Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genomic Engineering for Cell Therapy Development," three novel gene editing systems were used to make reproducible and efficient edits to human immune cells, demonstrating utility for the next generation of cell therapy development for blood cancers. Metagenomi’s novel gene editing systems were used to disrupt the T cell receptor alpha-chain constant region and the T cell receptor beta-chain constant region in approximately 90 percent of cells. Beta-2 microglobulin was edited in 95 percent of T cells. A chimeric antigen receptor (CAR) construct was also shown to be integrated in up to 60 percent of T cells. Novel gene editing systems were deployed in NK cells to disrupt CD38 — a cell surface immune modulator that can be targeted in the development of cancer immunotherapy — and to integrate a CAR construct that led to robust CAR-directed cellular cytotoxicity. B cell editing occurred in approximately 80% of target cells with successful transgene integration. What’s more, as these gene editing systems are taken from environmental samples as opposed to human pathogens, pre-existing immunity is expected to be rare. In summary, these novel systems were shown to result in highly efficient and specific gene edits in human immune cells and display the potential for use in cell therapy development.

Details of the presentations are below:

Presentation Title: A Novel Type V CRISPR System with Potential for Genome Editing in the Liver
Session Title: 801. Gene Therapies: Poster I
Presenting Author: Morayma Temoche-Diaz, PhD
Publication Number: 1862
Session Time: Saturday, December 11, 5:30 p.m. ET

Presentation Title: Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering for Cell Therapy Development
Session Title: 801. Gene Therapies: Poster III
Presenting Author: Gregory Cost, PhD, Vice President of Biology, Metagenomi
Publication Number: 3984
Session Time: Monday, December 13, 6:00 – 8:00 p.m. ET