He Dongsheng, Wagner Ernst
Pharmaceutical Biotechnology, Center for System-based Drug Research and Center for NanoScience (CeNS), Ludwig-Maximilians-University, 81377, Munich, Germany.
Macromol Biosci. 2015 May;15(5):600-12. doi: 10.1002/mabi.201400524. Epub 2015 Feb 5.
For successful gene therapy, the delivery of the curative genetic information into target cells is the main hurdle and the development of efficient and safe gene delivery carriers the crucial challenge. Polymeric materials have been widely investigated as gene delivery agents, generating first promising results. However, the heterogeneity and polydispersity of polymers and lack of site specific modifications make it difficult to achieve accurate structure-activity relationship studies. Moreover it will hamper manufacturing of highly defined materials which could be used in clinical development. Therefore, polymers with precise chemical structure are required. In this review, we focus on the current design of defined polymeric materials for gene transfer. We first discuss the barriers for gene delivery, and then provide examples which illustrate defined polymeric vectors, including dendrimers, peptide carriers, and sequence-defined oligoaminoamides.
对于成功的基因治疗而言,将治疗性遗传信息传递到靶细胞是主要障碍,而开发高效且安全的基因传递载体则是关键挑战。聚合物材料作为基因传递剂已得到广泛研究,并取得了初步的 promising 成果。然而,聚合物的异质性和多分散性以及缺乏位点特异性修饰使得难以进行准确的构效关系研究。此外,这将阻碍可用于临床开发的高度明确材料的制造。因此,需要具有精确化学结构的聚合物。在本综述中,我们重点关注用于基因转移的明确聚合物材料的当前设计。我们首先讨论基因传递的障碍,然后提供示例来说明明确的聚合物载体,包括树枝状大分子、肽载体和序列定义的寡聚氨基酰胺。