Scientist pipetting sample into a vial for DNA testing
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Gene editing firm Tome Biosciences has acquired startup Replace Therapeutics less than a month after Tome emerged from stealth with $213M in funding. This development adds fuel to an already hot field.

In early December, Vertex and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel [exa-cel]) for sickle cell became the first ever FDA-approved CRISPR/Cas9 genome-edited cell therapy. Axios reported that Morgan Stanley estimates sickle cell gene therapy treatments could reap $19B over the next decade.

Tome’s own proprietary gene editing technique inserts segments of DNA between 100 and 10000 megabases “precisely” the company says, and regardless of whether cells are dividing or not. Tome’s interest in Replace seems to be Replace’s DNA ligase technology. DNA ligases play a key role in DNA repair, replication, and recombination. 

Replace’s technology “combines the site-specificity of CRISPR/Cas9 with the writing enzyme DNA ligase to precisely manipulate small DNA sequences,” according to the Tome release.

Tome will pay Replace $65 million in upfront and near-term milestone payments and up to $185 million total in stock and cash. Replace will become a wholly-owned subsidiary of Tome Biosciences. 

The global gene editing market is estimated to be worth about $5B this year, and is expected to at least double over the next few years.

Replace is developing a novel programmable genomic integration (PGI) method for inserting and deleting small DNA sequences. This ligase-mediated PGI (L-PGI) technology, Tome says, is well-suited for 10s to 100s of base pair DNA edits, complementing Tome’s flagship large DNA PGI technology, integrase-mediated PGI (I-PGI). In in vitro studies, LPGI has demonstrated high efficiency and specificity in both dividing and non-dividing cells without the need for double-strand DNA breaks. 

“The addition of L-PGI to our PGI toolset provides us with the flexibility to choose the right editing tool for the right indication, expanding the types of diseases that we have the potential to cure,” said Rahul Kakkar, MD, president and CEO of Tome.

Halperin, founder and CEO of Replace, said,“We designed our ligase-mediated technology to make any DNA edit needed with a higher precision and efficiency than that seen with other DNA editing technologies. As a leader in PGI, Tome is well-suited to develop this technology for a multitude of different applications.” 

Tome was founded by two scientists with a new version of gene editing that was based on research licensed from the Massachusetts Institute of Technology. Kakkar, one of Tome’s co-founders, is the former CEO of autoimmune drugmaker Pandion Therapeutics, which sold to Merck & Co. for $2 billion two years ago.

Replace Therapeutics was founded by serial entrepreneur Shakked Halperin, PhD, whose previous company, Rewrite Therapeutics, was acquired by genome writing firm Intellia Therapeutics. Rewrite develops new tools for genome editing, including DNA writing via CRISPR/Cas9-guided polymerases.

Listen to Alex PhilippidisTouching Base podcast interview with Tome’s Rahul Kakkar, MD in episode 1: Launch of Tome Biosciences, AI scientist, mRNA vaccines.

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