Achieved therapeutically-relevant targeted gene integration and functional protein expression in vivo in non-human primates
Demonstrated efficient multiplex editing and integration of large DNA sequences with functional gene expression in iPSC-derived NK cells
Showed progress on lead programs: integrative gene therapy for phenylketonuria (PKU) and CD19/BCMA CAR-iNK for renal autoimmune diseases
WATERTOWN, Mass., May 10, 2024 (GLOBE NEWSWIRE) -- Tome Biosciences, Inc., the programmable genomic integration (PGI) company, today presented preclinical data highlighting its progress in developing PGI as integrative gene and cell therapies at ASGCT’s 27th Annual Meeting in Baltimore, MD.
“Our presentations at ASGCT provided a snapshot of the broad capabilities afforded by PGI technologies, from rapid, efficient and multiplex editing of iPSCs and HSCs to targeted integration of functional genes at therapeutically-relevant levels in non-human primates,” said John Finn, PhD, Chief Scientific Officer of Tome.
The Company is developing two technologies capable of PGI: integrase-mediated PGI (I-PGI), which is best suited for integrating large DNA sequences (>1,000 base pairs) and ligase-mediated PGI (L-PGI), which is best suited for integrating small DNA sequences (1-100s of base pairs). I-PGI works by first inserting a unique sequence into the genome in a user-defined location. This sequence provides a beacon for a proprietary integrase to recognize and subsequently insert the provided DNA sequence of interest. L-PGI can insert any small template DNA sequence into the genome ata user-defined location. Both technologies can edit the genome without depending on a double stranded DNA break.
Progress on these technologies was presented at ASGCT.
Unveiled the Company’s lead programs in integrative gene therapy as PKU and cell therapy as a CD19/BCMA CAR-iNK for renal autoimmune diseases.
Reported progress on liver technical development for PKU, demonstrating efficient I-PGI gene integration and functional gene expression across multiple loci and transgenes in vitro in primary human hepatocytes and in vivo in mice and non-human primates. In all cases, including the early non-human primate data, the Company has achieved potentially curative editing efficiencies for PKU.
Reported progress on the Company’s CD19/BCMA CAR-iNK program, showing efficient I-PGI integration of 12,000 base pairs into iPSCs, and demonstrating functional expression in the differentiated iNK of genes designed to enhance the efficacy and convenience of an autoimmune cell therapy, with the ability to re-dose and reverse the treatment. The data presented included both in vivo evidence of CD19 killing in mice and in vitro B cell killing in blood samples from patients with lupus.
Reported on previously undescribed challenges with reverse transcriptase-mediated writing of long (~40bp) sequences in rodent non-dividing cells and potential solutions.
Showcased the ability of I-PGI to efficiently edit iPSCs and HSCs, including integrating >30,000 base pairs and multiplexing four different genes at four different loci, which enables the rapid creation of complex cell circuitry.
Reported the development of proprietary assays designed to detect potential off-target editing of integrases, including double stranded breaks (DSBs), indels, cryptic integrations and chromosomal rearrangements.
Demonstrated L-PGI efficiently edited primary human hepatocytes in vitro across multiple therapeutically-relevant genomic loci, and these edits showed higher fidelity versus DNA edits using reverse transcriptase.
Copies of the posters and presentations will be available on Tome’s website, www.tome.bio, following the conference.
About Tome Tome Biosciences, Inc., is the programmable genomic integration (PGI) company. Our technologies allow us to insert any genetic sequence of any size at any location in the genome with site-specific precision. We are writing the final chapter in genomic medicines, delivering cures to patients through cell and integrative gene therapies. Follow us on X @Tome_Bio and on LinkedIn. www.tome.bio.
PGI™, I-PGI™ and L-PGI™ are brand names and technologies of Tome Biosciences, Inc.
