【摘要】 近年来,按照药品研发并申报临床试验的细胞治疗产品大量涌现,其研发技术与评价体系处于快速发展阶段。基因转导系统包括逆转录病毒、慢病毒、腺病毒等病毒载体和转座子、TALEN、CRISPRCas9等非病毒载体基因编辑系统等,广泛应用于不同种类细胞的改造。由于基因转导系统在细胞内表达、组装、转导、基因整合的作用机制复杂,对其人体应用的科学评价构成了挑战。结合近期细胞治疗产品临床试验申报资料审评和沟通交流过程中出现的问题,参考国内外相关技术指导原则,本文围绕基因转导系统中慢病毒和转座子的设计和安全性评估,提出现阶段的药学审评考虑点,供研发者和监管方讨论交流。更多还原

【Abstract】 The number of Investigational New Drug( IND) Applications of cellular products largely increased in recent years. Meanwhile,the researches and evaluations of cellular products develop rapidly. Gene transduction systems are widely used to transduce genes into different types of cells,including retrovirus,lentivirus,adenovirus,other viral vectors,as well as transposons,TALEN,CRISPR-Cas9 and other non-viral gene editing systems. The scientific evaluation of gene transduction systems for human use is challenging due to the complex mechanisms in terms of expression,assembly,transduction and gene integration. Regarding the problems recently occurred in the review process of IND dossiers and pre-IND consultations of cell therapy products,this article summarized the assessment of design and safety for lentivirus and transposon transduction systems,and proposed CMC review considerations referring to the relevant technical guidelines,hoping to improve the communications between developers and regulators.更多还原