CREATE Medicines Unveils ‘RetroT’ All-RNA Gene Writing System for Safer and Site-Specific T-Cell Engineering

CAMBRIDGE, Mass., October 29, 2025 — CREATE Medicines, Inc. (formerly Myeloid Therapeutics) today announced a major breakthrough in gene editing, presenting new preclinical data on its RetroT system—a fully RNA-encoded, site-specific gene-integration platform. The results, highlighted at the Cold Spring Harbor Laboratory Meeting on Immune Engineering & Cellular Immunotherapy, demonstrate the successful and precise delivery of therapeutic payloads into T cells without relying on traditional viral vectors, DNA templates, or creating hazardous double-strand DNA breaks (DSBs).

Key Advance: Harnessing the Human Genome’s ‘Jumping Gene’

RetroT distinguishes itself by utilizing the human cell’s own LINE-1 retrotransposon—the body’s only active “jumping gene”—to drive programmable, multi-kilobase gene insertion. This natural mechanism, combined with a CRISPR-based nickase, allows for the precise, site-specific integration of a desired genetic payload.

“RetroT reframes what’s possible, a purely RNA-based system that programs T cells in vivo with site-specific, durable gene insertion while maintaining the flexibility to re-dose,” said Dr. 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.”

Superior Genomic Safety and CAR Delivery Confirmed

The presented study validated the platform’s potential by successfully inserting a CD19-CAR transgene into human T cells, a crucial step for developing next-generation CAR T-cell therapies.

The core advantage of RetroT is its superior genomic safety profile:

• No Double-Strand Breaks (DSBs): By avoiding DSBs, the system significantly reduces the risk of genotoxicity and off-target chromosomal rearrangements commonly associated with traditional CRISPR/Cas9 methods.
• Precise Integration: Sequencing confirmed that the RetroT engineered T cells exhibited precise integration with no detectable off-target effects, partial insertions, or genomic scars.
• Cell Functionality: The modified T cells maintained full functionality and viability, demonstrating target-specific cytotoxicity while preserving cell fitness and phenotype.

This purely RNA-based approach has the potential to transform precision in vivo gene editing by making the process safer, more scalable, and less toxic to the engineered cells.

Advancing the Multi-Immune Programming Platform

CREATE Medicines continues to build upon its multi-immune programming platform, which is designed to selectively program T cells, myeloid cells, and NK cells directly within the body.

The company’s pipeline is focused on developing next-generation in vivo CAR therapies for solid tumors and autoimmune diseases, supported by their validated LNP delivery platform and proprietary RNA engineering expertise.