CREATE Medicines, Inc. has presented new preclinical data for RetroT, the company’s fully RNA-encoded, site-specific gene-integration system, at the Cold Spring Harbor Laboratory Meeting on Immune Engineering & Cellular Immunotherapy.
The results highlight precise integration of therapeutic payloads without double-strand DNA breaks, viral vectors, or DNA templates, supporting a path to safer, scalable in vivo cell engineering.
“RetroT reframes what’s possible, a purely RNA-based system that programmes T cells in vivo with site-specific, durable gene insertion while maintaining the flexibility to re-dose,” said Robert Hofmeister, chief scientific officer of CREATE Medicines.
“When combined with our targeted LNP delivery and human-validated mRNA platform, RetroT provides a direct and scalable path to clinical proof of concept.”
By harnessing the natural mobility of the LINE-1 retrotransposon and a CRISPR-based nickase, the company said results demonstrate that RetroT achieves site-specific integration of genetic payloads into immune cells. This approach has the potential to transform precision in vivo gene editing by reducing off-target effects and genotoxicity associated with traditional CRISPR/Cas9 methods.
In the presented study, CREATE Medicines used RetroT to successfully insert a CD19-CAR transgene into human T cells. RetroT uses the LINE-1 retrotransposon, the only active “jumping gene” in the human genome, to integrate genetic payloads without double-strand DNA breaks, viral vectors, or DNA payloads. RetroT engineered T cells show full functionality and target-specific cytotoxicity while preserving cell fitness and phenotype. Sequencing confirmed precise integration with no detectable off-target effects, partial insertions, or genomic scars.
CREATE Medicines said it continues to advance its multi-immune programming platform, which enables selective programming of T cells, myeloid cells, and NK cells directly within the body. The company’s pipeline includes next-generation in vivo CAR therapies for solid tumours and autoimmune diseases, supported by a validated LNP delivery platform and proprietary RNA engineering.
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