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RetroT CAR T cells represent a novel platform technology developed by CREATE Medicines (formerly Myeloid Therapeutics) for the generation of next-generation CAR T-cell therapies. The RetroT system is an all-RNA, non-viral, site-specific gene-integration platform that utilizes human LINE-1 retrotransposon machinery in combination with a CRISPR-based nickase. This approach allows for the programmable integration of CAR transgenes into T cells without the need for double-strand DNA breaks, viral vectors, or DNA templates, thereby reducing genotoxic risks. The technology is designed for in vivo immune cell programming, delivered via mRNA-lipid nanoparticles (LNPs). Preclinical studies have demonstrated that RetroT can successfully insert CD19-CAR transgenes into human T cells, resulting in potent, antigen-specific cytotoxicity and significant tumor reduction in leukemia models. The platform is currently being developed for applications in solid tumors, hematologic malignancies, and autoimmune diseases.
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