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You have full access to this article via your institution. Download PDF Tome Biosciences has debuted with $213 million to bring their genome-editing platform to the clinic. The technology
can insert large DNA sequences into the genome in any position to correct genes in vivo. The tool, dubbed PASTE — programmable addition via site-specific targeting elements — was developed
by Tome co-founders Omar Abudayyeh and Jonathan Gootenberg from the Massachusetts Institute of Technology. Investors include Andreessen Horowitz, Arch Venture Partners, Polaris and Fujifilm.
PASTE uses a CRISPR–Cas9 nickase fused with two other enzymes: a reverse transcriptase and a serine integrase. The guide RNA-directed reverse transcriptase creates landing sites for the
serine integrase, which inserts large sequences of DNA. Tome has shown that its tool can insert sequences of ~36 kb in various dividing and non-dividing cell types. And, unlike other editing
tools, it doesn’t rely on repair responses to the double-strand breaks that can result in insertions, deletions and off-target effects. Tome initially plans to develop this technology as
gene therapies for monogenic liver diseases and cell therapies for autoimmune diseases. In gene therapies, PASTE could insert a whole wild-type gene without the need to be tailored to
specific mutations, while in cell therapies, engineered genes might be added at precise loci. Shortly after debuting, Tome acquired startup Replace Therapeutics for $65 million, adding
another genomic integration tool to its repertoire. Replace’s technology is like PASTE, except the integrase is replaced by a DNA ligase that inserts short DNA sequences. RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tome launches CRISPR tool for oversized DNA. _Nat Biotechnol_ 42, 163 (2024).
https://doi.org/10.1038/s41587-024-02152-z Download citation * Published: 15 February 2024 * Issue Date: February 2024 * DOI: https://doi.org/10.1038/s41587-024-02152-z SHARE THIS ARTICLE
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