BASIC Enables Selection-Free Efficient Knock-In of Large DNA in Primary Human T Cells

作者: Kexin Wang, Xiaorui Li, Jin Li, Zhuoying Yu, Pan Li, Yuyang Xie, Jinxin Liu, Honglin Huang, Shanshan Zhang, Mengqiao Zhang, Wenju Ma, Fei Gao, Xuguang Du, Jianxun Wang, Mario R. Capecchi, Sen Wu
杂志: Molecular Therapy
Doi: https://www.doi.org/10.1016/j.ymthe.2025.12.064
出版日期: 2026/1/2

论文中使用的产品/服务

摘要

Efficient and precise insertion of large DNA fragments into primary human T cells has remained a bottleneck for gene and cell therapy. We present BaEVshort-AAV6 site-specific integration for CAR T (BASIC), a modular platform that combines BaEVshort-pseudotyped virus-like particles for Cas9 RNP delivery with AAV6 donor vectors for homology-directed repair. BASIC achieves >85% knockin efficiency without drug selection or electroporation, preserving cell viability while enabling multiplex genome engineering. Edited chimeric antigen receptor (CAR)-T cells show uniform CAR expression, enhanced cytotoxicity, and complete tumor clearance in vivo. BASIC offers a clinically scalable solution for next-generation cell therapies.

文章链接

关于派真

作为一家专注于AAV 技术十余年，深耕基因治疗领域的CRO&CDMO，派真生物可提供从载体设计、构建到 AAV、慢病毒和 mRNA 服务的一站式解决方案。凭借深厚的技术实力、卓越的运营管理和高标准的服务交付，我们为全球客户提供一站式CMC解决方案，包括从早期概念验证、成药性评估到IIT、IND及BLA的各个阶段。

凭借我们独立知识产权的π-alpha^TM 293 细胞AAV高产技术平台，我们能将AAV产量提高多至10倍，每批次产量可达1×10¹⁷vg，以满足多样化的商业化和临床项目需求。此外，我们定制化的mRNA和脂质纳米颗粒（LNP）产品及服务覆盖药物和疫苗开发的各个阶段，从研发到符合GMP的生产，提供端到端的一站式解决方案。