诺奖团队进军in vivo CAR-T，利用新型包膜递送载体，在体内直接生成CAR-T细胞

Core Viewpoint - Azalea Therapeutics, co-founded by Nobel laureate Jennifer Doudna, is entering the competitive in vivo CAR-T field with a focus on innovative gene therapy solutions and a new delivery technology platform [2][3]. Funding and Development Plans - On November 4, 2025, Azalea announced a funding round of $82 million to advance an in vivo CAR-T cell therapy for B-cell malignancies into clinical stages within the next 12-18 months [2]. - The company aims to further develop its novel delivery technology platform [2]. Technology and Innovation - Azalea's core asset is the Enveloped Delivery Vehicle (EDV), a delivery technology developed in Doudna's lab, which was published in Nature Biotechnology in January 2024 [3]. - The EDV utilizes a modified vesicular stomatitis virus glycoprotein (VSVGmut) paired with antibody-derived single-chain variable fragments (scFv) to package Cas9 ribonucleoprotein complexes for targeted genome editing [5][7]. Advantages of EDV - Unlike traditional delivery systems, EDV allows for predictable antibody-antigen interactions, enabling selective and instantaneous delivery of genome editing components to target cells [7]. - In mixed cell populations, Cas9-EDV preferentially edits the genome in target cells without off-target effects in liver cells, establishing a programmable delivery strategy with broad therapeutic potential [7]. Founding Team and Expertise - The founding team includes Michael Fischbach and Justin Eyquem, with Eyquem contributing a second delivery vehicle for in vivo CAR-T therapy [9]. - Eyquem's previous research demonstrated that integrating CAR into the TRAC gene locus reduces potential oncogenic risks and enhances anti-tumor activity [9]. Upcoming Presentations and Industry Context - Azalea plans to present a series of proof-of-concept data from tumor mouse models at the upcoming ASGCT conference, with experiments in primate models also underway [10]. - The in vivo CAR-T sector has seen significant activity in 2023, with multiple acquisitions and advancements from major companies, indicating a rapidly evolving landscape [11][12][13][14].