基因治疗用质粒DNA生产面临的问题及研究进展

基因治疗已成为21世纪一些重大疾病的有效治疗策略,目前携带治疗基因的重组质粒已作为基因药物进入临床研究。对用于基因治疗的生物制品的生产与质量控制都有相当严格的要求。虽然已建立大规模符合药学规格的质粒DNA生产工艺,能满足临床需求,但在这些生产工艺中还存在一些难以克服的瓶颈,如:载体构建、细胞裂解、细菌染色体DNA去除、细菌内毒素去除、生产过程中质量控制等。就近年来大规模生产临床用质粒DNA遇到的相关问题及解决方案作一综述。

Research Progress in Large-scale Production of Plasmid DNA for Gene Therapy

Plasmid DNA encoding treatment gene for pharmaceutical applications was approved into the clinical trials. A pre-requisite to the success of plasmid-based therapies is the development of effective production of plasmid DNA. However, at present, there are several problems and bottlenecks in large-scale production of pharmaceutical plasmid DNA. Such as vector construction, cell lysis, bacteria chromosome DNA removing, bacteria endotoxin removing and quality-control in production process. The downstream for the large-scale production of plasmid DNA, limitations and the strategies used to obtain a final product that meets specifications was reviewed.