Vita：马丽佳/李颜团队开发新型AAV，打一针，在体内自动生成CAR-T细胞，治疗系统性红斑狼疮

Core Viewpoint - CAR-T cell therapy is a revolutionary cancer treatment that utilizes genetically modified T cells to target and kill cancer cells, and it has shown promise in treating autoimmune diseases as well [2]. Group 1: Challenges of Traditional CAR-T Therapy - The preparation of CAR-T therapy is complex and expensive, involving blood extraction, genetic modification, and expansion, which can take several weeks and incur high costs [3]. - A pre-treatment with chemotherapy is required to clear the patient's existing lymphocytes before reinfusion, leading to significant side effects [3]. Group 2: Innovations in CAR-T Therapy - Researchers have proposed in vivo CAR-T cell therapy, which allows for the direct generation of CAR-T cells in the body through injection, potentially simplifying and broadening access to CAR-T therapy [4]. - A study published on February 3, 2026, introduced a novel adeno-associated virus variant, AAV6-M2, which can specifically target human T cells and generate CAR-T cells effectively in a mouse model of systemic lupus erythematosus (SLE) [4][5]. Group 3: Mechanism and Efficacy - The AAV6-M2 variant was developed using AI-assisted design and high-throughput screening, allowing it to efficiently target resting T cells without prior activation, which is crucial for in vivo CAR-T cell generation [8]. - In tests on humanized mouse models, a single injection of AAV6-M2-CD19CAR led to a 77.5% conversion rate of CD8+ T cells to CAR-T cells, effectively eliminating B cells and improving symptoms of lupus [10]. Group 4: Safety and Advantages - AAV6-M2 demonstrated significantly reduced liver tropism compared to wild-type AAV, lowering the risk of liver toxicity and enhancing the cost-effectiveness of the treatment [13]. - The study indicates that AAV-mediated CAR delivery can generate functional human CAR-T cells in vivo, marking a shift from personalized treatments to more universal, off-the-shelf products [5][14]. Group 5: Future Prospects - This research signifies a platform innovation, proving that a single systemic injection of an AAV vector can generate durable, functional human CAR-T cells, paving the way for rapid clinical translation [14]. - The application of AAV-mediated gene therapy is expanding from genetic diseases to cancer and autoimmune diseases, opening new avenues for accessible cell and gene therapies [15].