Programmable Gene insertion (PGI) is the ability to insert a given genetic sequence at a user-defined location in the genome with site-specific precision. PGI is a revolutionary approach for the development of potentially curative cell and integrative gene therapies.
Efficiently and directionally insert DNA sequences in a manner not dependent on DNA double stranded breaks (DSB)

Insert DNA sequences ranging in size from 1-10,000+ bases

Place sequences precisely where they are programmed to go
Place multiple sequences simultaneously (i.e., multiplex insertions)
Edit dividing and non-dividing cells
Minimize potential for off-target events

PGI can be accomplished utilizing several different enzyme architectures which have in common the specificity of CRISPR/Cas9 nickases to direct an intended genomic insertion to a desired location.

Tome is currently developing two PGI technologies: integrase-mediated PGI (I-PGI) and ligase-mediated PGI (L-PGI).

Because our technology is programmable, we can choose precisely where in the genome we insert genetic sequences. This capability affords ultimate flexibility to reprogram regions of the genetic code, with broad-ranging implications across all therapeutic areas, as integrative gene therapies and as cell therapies.​

For integrative gene therapies, we can patch a healthy gene into its native circuitry, allowing for natural protein expression at the right amount, at the right time and by the right cell. Alternatively, we can link a transgene to any gene in the cell, giving us unparalleled flexibility with respect to expression levels and timing. Our initial focus for integrative gene therapies​ is on monogenic liver diseases.
For cell therapies,​ we can rewire entire cell circuitry by simultaneously inserting multiple genes in multiple locations. Through the highly-efficient, multiplexed deletion and insertion of genes, PGI allows us to create complex cell therapies with ease. This is a quantum leap in cell therapy design and discovery, which unlocks applications in common diseases, beginning with autoimmunity.
PGI is a powerful technology platform which unlocks the full potential of genome engineering, representing the final chapter in genomic medicines.
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I-PGI works by placing a “beacon” in the genome, which is a unique integrase recognition site, at the target locus. The beacon sequence has no known homology to human DNA, which allows for the specific insertion of the DNA sequence of interest and reduces the potential for off-target integration. Our proprietary integrase recognizes this beacon and inserts the DNA sequence of interest at the beacon site. Not only is this entire process highly efficient, it is agnostic to the size of the DNA insert, and avoids double stranded breaks in the DNA, minimizing the risk of translocation events.


L-PGI utilizes DNA ligase to perform a number of different DNA edits, including correcting point mutations and inserting or deleting DNA sequences of up to 100s of base pairs. This technology has a number of advantages for DNA editing:

  1. Equal efficiency in dividing and non-dividing cells
  2. Improved efficiency over other small DNA editing technologies
  3. High editing accuracy