Recently,an important research achievement, entitled 《BASIC Enables Selection-Free Efficient Knock-In of Large DNA in Primary Human T Cells》, has been published online in 《Molecular Therapy》 the internationally authoritative journal of gene and cell therapy. This study proposes a groundbreaking gene-editing platform BASIC, which provides a novel solution for the engineering and scaling of next-generation cell therapies.
One of the corresponding authors of the paper is Professor Jianxun Wang, currently the Chief Scientist of Shenzhen Cell Valley, who has long been dedicated to the research of key technologies in gene editing and cell therapy. This study was also co-corresponded by Professor Mario R. Capecchi, the 2007 Nobel Prize laureate in Physiology or Medicine, and Professor Sen Wu from China Agricultural University, highlighting the high recognition and significant status of this achievement in the international academic community.
Breaking the Bottleneck Challenges in Cell Therapy
The precise and efficient integration of large therapeutic genes into primary human T cells has long been a core challenge in the industrialization of cell therapy. Conventional methods often rely on electroporation or random viral integration, which not only limit efficiency but may also cause cell damage and pose potential safety risks.
The BASIC platform proposed in this study innovatively combines BaEVshort enveloped virus-like particles (VLPs) with the AAV6 donor vector, achieving one-step precision gene editing without electroporation or drug screening.
Studies have demonstrated that the platform achieves the following in primary human T cells:
· Over 85% CAR site-directed knock-in efficiency
· Over 95% gene knockout efficiency
· High cell viability and highly consistent CAR expression
Significantly enhance CAR-T functionality and safety
The CAR-T cells constructed on the BASIC platform demonstrated enhanced tumor-killing capacity and reduced expression of functional failure markers in both in vivo and in vitro experiments. In mouse models, they achieved complete tumor clearance and 100% survival rate, significantly outperforming the traditional lentiviral CAR-T technology approach.
Furthermore, the platform supports simultaneous multi-gene editing and has been successfully extended to NK cells, laying a critical technical foundation for the development of universal and off-the-shelf cell therapy products.
International collaboration for clinical translation
Professor Wang Jianxun stated that this research is not only a significant breakthrough in basic research, but also an engineering solution oriented towards clinical and industrial applications. Shenzhen Cell Valley will continue to promote the translational application of related technologies in CAR-T, CAR-NK, and other cell and gene therapy products, accelerating the international clinical stage of China's original technologies.
Professor Mario R. Capecchi, Nobel laureate in Physiology or Medicine in 2007, is a professor in the Department of Human Genetics at the University of Utah. His pioneering work on mammalian gene homologous recombination and gene targeting technologies laid the foundation for modern gene editing and transgenic animal research, which has been widely applied in the study of human disease mechanisms and gene therapy.
Professor Wu Sen, a professor and doctoral supervisor at China Agricultural University, has long been engaged in research on gene editing, viral-like particle (VLP) delivery technology, and molecular design breeding. He has achieved systematic and original results in CRISPR-Cas systems, precise gene knock-in, and their applications in animal and plant cell therapy. Multiple studies have been published in internationally authoritative journals such as Molecular Therapy.
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