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西湖大学开发基因递送黑科技,全球首个哺乳动物蛋白凝聚体递送系统丨ASGCT 口头报告精选
生物世界· 2025-05-26 02:52
Core Viewpoint - The EASY system, developed by Westlake University and the Westlake Coacervate Research Team, is a novel non-viral, non-liposomal nucleic acid delivery platform that has been recognized at the American Society of Gene & Cell Therapy (ASGCT) annual meeting, highlighting its potential in gene delivery applications [1][3][19]. Group 1: Introduction to EASY System - The EASY system is the first mammalian coacervate-based delivery system, designed to efficiently deliver various types of nucleic acids, including plasmid DNA, mRNA, and CRISPR-Cas9 tools [1][5]. - The system is inspired by natural cellular coacervates, which are membrane-less organelles formed through liquid-liquid phase separation, playing crucial roles in various biological processes [6]. Group 2: Mechanism and Advantages - The core of the EASY system is the engineered endogenous protein, ProteanFect™, which self-assembles with nucleic acids to form highly ordered nanoparticle structures [7]. - The delivery process involves the formation of stable nanoparticles, efficient cellular uptake through active endocytosis, intracellular release of nucleic acids, and safe degradation of carrier proteins via natural cellular pathways [8]. - The EASY system offers revolutionary advantages, including: 1. Ultra-high loading capacity, approximately 50 times that of lipid nanoparticles (LNP) [9]. 2. Compatibility with various nucleic acids, enabling the delivery of plasmid DNA, mRNA, siRNA, sgRNA, and Cas9 mRNA [10]. 3. High efficiency and low toxicity, achieving comparable or higher gene delivery efficiency while significantly reducing cell mortality [10]. 4. Broad applicability to various primary cells, including NK cells, B cells, and hematopoietic stem cells [10]. Group 3: Commercialization and Clinical Relevance - The ProteanFect series of kits represents the first commercial product of the EASY system, enabling efficient gene delivery and precise gene editing in various primary and hard-to-transfect cells [13]. - The system has demonstrated high gene editing efficiency in primary T cells, with results showing a range of 67%-88% efficiency for gene marking and over 90% efficiency for gene editing [18]. Group 4: Future Outlook - As gene therapy approaches critical clinical applications, the safety and efficacy of delivery systems are paramount. The EASY system provides a new solution by leveraging the natural biological mechanisms of coacervates [19]. - The international recognition of this technology not only affirms China's scientific innovation but also brings new hope to the global gene therapy field, with expectations for the EASY system to play an increasingly important role in clinical applications [19].