摘要
在基因治疗领域中,如何设计并制备出一种相容性好、转染效率高和细胞毒性低的基因载体,并将其应用于基因传递过程一直是人们研究的热点。当前,基因载体主要分为病毒类和非病毒类两大类型。在临床治疗中,病毒类载体的转染效率较高,但由于其存在整体安全性较低、制备工艺复杂和易引发免疫应答反应等缺点,大大限制了其在基因治疗中的应用。非病毒类载体聚β-氨基酯(PBAEs),是利用迈克尔加成反应机理,由胺和丙烯酸酯类单体合成的一种聚合物,具备高细胞活性、低细胞毒性、原料易得、合成简单以及结构多样等优点,是一类有广阔应用前景的非病毒基因载体材料。近年来,随着聚β-氨基酯研究的深入,众多的改进方法被应用于对其结构的改性优化,从而使其性能得到了持续的提升。主要从枝化、封端、侧链修饰、末端修饰以及嵌段修饰5个方面对聚β-氨基酯的改性研究进展进行了综述,并且对聚β-氨基酯的工业化生产和质量控制进行了讨论,为基因治疗领域的研究提供参考。
The design and development of gene carriers with excellent biocompatibility,high transfection efficiency,and low cytotoxicity,as well as their application in gene delivery,remain key research focuses in gene therapy.Currently,gene vectors are mainly divided into viral and non-viral types.Viral vectors offer high transfection efficiency in clinical applications;however,their application is significantly limited by safety concerns,complex manufacturing processes,and the risk of eliciting immune responses.Poly(β-amino esters)(PBAEs)are a class of non-viral vectors synthesized via the Michael addition between amine and acrylate monomers.They offer advantages such as high cellular activity,low cytotoxicity,readily available raw materials,straightforward synthesis,and structural diversity,positioning them as promising candidates for non-viral gene delivery.In recent years,research on PBAEs has advanced,with numerous modification strategies applied to optimize their structures and improve their performance.This review summarized progress in five major modification approaches:branching,capping,side chain modification,end-group modification,and block copolymerization.Furthermore,industrial-scale production and quality control of PBAEs were discussed.This review aimed to provide valuable insights and references for research within the gene therapy domain.
作者
张博
袁梓诺
陈绮琪
曾明
李湘
熊梧琬
ZHANG Bo;YUAN Zi-nuo;CHEN Qi-qi;ZENG Ming;LI Xiang;XIONG Wu-wan(College of Environmental and Chemical Engineering,Zhaoqing University,Zhaoqing 526061,China;Department of Dermatology,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China)
出处
《化学试剂》
2025年第9期63-72,共10页
Chemical Reagents
基金
肇庆学院博士启动基金项目(221865)
肇庆学院大学生创新创业计划项目(X202410580140S)。
关键词
聚β-氨基酯
阳离子聚合物
基因载体
改性
转染效率
poly(β-amino esters)
cationic polymer
gene vectors
modification
transfection efficiency
