Methods of editing the genome are powering the development of new cell and gene therapies for diseases that have been challenging to treat. Companies like Tome Biosciences are part of a wave of startups building commercial platforms that leverage CRISPR/Cas9 and other genome editing technologies.
Earlier this week, Tome raised $213 million in Series A and B funding from investors including Andreessen Horowitz (a16z) Bio + Health, ARCH Venture Partners, GV, Longwood Fund, Polaris Partners, Bruker Corporation, FUJIFILM Corporation, and Alexandria Venture Investments. The funds will support Tome’s efforts to develop and commercialize programmable genomic integration (PGI) technology that was in-licensed from the Massachusetts Institute of Technology (MIT).
PGI combines CRISPR with enzymes that can insert or write DNA sequences as long as a gene into the genome without requiring double-strand DNA breaks. Tome’s portfolio includes integrase-mediated PGI (I-PGI), which utilizes proprietary integrases to precisely insert large sequences into the genome. I-PGI tech is based on the programmable addition via site-specific targeting elements (PASTE) approach to genome editing, first discovered at MIT by Tome’s co-founders Omar Abudayyeh, PhD, and Jonathan Gootenberg, PhD.
Details of PASTE are provided in a Nature Biotechnology paper that was published in 2022 titled, “Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases.”
To date, Tome has demonstrated that I-PGI can insert more than 30kb of genetic code at desired sites in different types of dividing and nondividing cell types, and it can be multiplexed. “The ability to control where we insert DNA sequences is a game-changer. It means the field can now move away from random integration and utilize any natural promoter in the human genome, enabling us to orchestrate the tissue location, timing and amount of gene expression,” noted John Finn, PhD, Tome’s CSO.
Tome initially plans to use the PGI tech to develop integrative gene therapies for monogenic liver diseases and cell therapies for autoimmune diseases. “PGI represents the maturation of editing technologies, breaking current barriers in genomic medicines discovery,” said Rahul Kakkar, MD, Tome’s president and CEO. “For patients with rare monogenic diseases, PGI allows for potentially curative treatments with a single drug per disease regardless of genetic heterogeneity, and for patients with more common disorders, PGI allows for the creation of cell therapies at the speed of biologics discovery with a complexity that enables the potential for broad use across human medicine.”