已上市基因治疗产品的非临床研究分析

Non-clinical analysis of marketed gene therapy products

基因治疗产品通过所转导遗传物质的转录或翻译而发挥作用,基于蛋白的疗法需要反复给药,而如果可修复病人的错误基因或直接提供正确的基因,那么单次治疗就有可能产生持续的治疗效果。随着基因治疗的突破性发展,为某些罕见疾病(尤其是单基因遗传病)提供了一次治愈的可能,或将成为未来治疗人类疾病的重要手段。国家药品监督管理局于2021年12月发布了《基因治疗产品非临床研究与评价技术指导原则》,为基因治疗产品的研发提供建议,以支持开展相应的临床试验。本文回顾和梳理了已上市的3种基因治疗产品所开展的非临床研究,并分别从药理学、药代动力学和毒理学等方面对基因治疗产品非临床评价的关注要点进行分析和探讨,供研究者关注或参考。

Gene therapy products work through the transcription or translation of the genetic material being transferred. Protein-based therapies require repeated dosing, whereas if a patient’s faulty gene can be fixed or the correct gene can be delivered directly, a single treatment may have a lasting effect.With the breakthrough development of gene therapy, it provides the possibility of a cure for some rare diseases(especially single gene genetic diseases), or it will become an important means to treat human diseases in the future. In December 2021, the National Medical Products Administration issued the Guideline for Non-clinical Research and Evaluation of Gene Therapy Products to provide suggestions for the development of gene therapy products and support clinical trials.In this paper, the non-clinical studies of three gene therapy products on the market were reviewed and summarized, and the key points of non-clinical evaluation of gene therapy products were analyzed and discussed from the perspectives of pharmacology, pharmacokinetics and toxicology, so as to draw attention or provide reference for researchers.