Circular Single-Stranded DNA Enables Efficient Non-Viral Immune Cell Engineering: Implications for CAR-T Cell Therapy

Scientists developed a novel circular single-stranded DNA technology that enables highly efficient gene integration in various cell types, achieving up to 70% successful gene integration. The system can carry genetic sequences of up to 20 kb in length, showing promise for CAR-T cell therapy development.

By: Christos Evangelou - Dec. 11, 2024

In a recent study, scientists at Full Circles Therapeutics developed a novel DNA template system to engineer immune cells for therapeutic purposes. The researchers demonstrated that their novel mini-circular single-stranded DNA (cssDNA) technology, termed GATALYST, enables more efficient and safer genetic modifications in various cell types, including induced pluripotent stem cells (iPSCs) and immune cells used in cancer immunotherapy. The system achieved up to 70% gene integration in some cell types while maintaining high cell survival rates.

"When we use conventional double-stranded DNA as a donor, we typically achieve only single-digit percentage integration rates. However, with cssDNA, we can achieve much higher efficiency, with integration rates of 50%–70%,“ said Howard Wu, PhD, co-founder and CSO at Full Circles Therapeutics, and corresponding author of the study. »This higher efficiency saves significant time and resources, potentially reducing the cost of therapeutic products. Ultimately, this makes the treatment more affordable and accessible to patients.«

The study was published in Nature Biotechnology.

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