#United States #Cambridge #CREATE Medicines #RNA-based therapy #T-Cell Engineering

CREATE Medicines Revolutionizes T-Cell Engineering with RetroT

CREATE Medicines, previously known as Myeloid Therapeutics, has announced significant advancements in the field of T-cell engineering with the introduction of RetroT, a unique fully RNA-encoded gene integration system. Presented at the Cold Spring Harbor Laboratory Meeting on Immune Engineering, the preclinical data showcases RetroT's ability to perform site-specific, durable gene integration in T-cells without the use of traditional methods, such as double-strand DNA breaks. This development aims at enhancing the safety profile and scalability of continued in vivo therapies, crucial for cancer treatment and other diseases.

In essence, RetroT takes a significant leap by utilizing human LINE-1 machinery, which allows for programmed integration of sizable gene payloads directly into immune cells. This innovative approach minimizes the risks associated with off-target effects typically seen in conventional CRISPR/Cas9 applications.

According to Dr. Robert Hofmeister, Chief Scientific Officer at CREATE Medicines, the RetroT system essentially redefines what is achievable in cellular engineering. "This RNA-based technology not only ensures precise genetic programming of T cells but also allows for the flexibility needed to deliver multiple doses effectively," he commented. The implications of this technology are vast, paving the way for more controllable and effective gene therapies.

During their studies, CREATE Medicines successfully integrated a chimeric antigen receptor (CD19-CAR) transgene into human T-cells. This successful application demonstrates that T-cells engineered using RetroT retain full functionality and target specificity, which is essential for effective immunotherapy treatments. The precise integration was confirmed through sequencing, showing no off-target modifications or genomic alterations, thereby asserting a crucial advancement in genetic safety.

The innovative RetroT platform aligns with CREATE Medicines' broader goal of developing a multi-immune programming system that can target T-cells, myeloid cells, and NK cells within the patient's body. CREATE Medicines is also actively advancing next-generation CAR therapies aimed at treating solid tumors and autoimmune conditions, backed by their state-of-the-art RNA engineering and LNP delivery strategies.

For those interested in new advancements in genetic engineering, RetroT presents a landmark shift in how genetic therapies could evolve, especially in scenarios demanding high safety standards. The potential market for such treatments, focusing on cancer and other chronic illnesses, could see substantial changes with the effective execution of RetroT technology.

Additionally, to provide further context about RetroT, the findings were elaborated in a peer-reviewed publication titled CRISPR-Enabled Autonomous Transposable Element (CREATE) for RNA-based gene editing and delivery, appearing in EMBO Reports earlier this year (Wang et al., EMBO Rep (2025), 261062–1083).

Overall, CREATE Medicines remains at the forefront of biotechnology innovation, with RetroT positioning itself as a foundational pillar for the future of safely managed immunotherapies. Their ongoing commitment to advancing in vivo CAR therapies is set to redefine treatment standards across various diseases and pave the way for more effective patient outcomes.

For more details, visit CREATE Medicines' official page and stay abreast of their latest advancements in immune programming therapies.