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Multivalent Peptide-Functionalized Bioreducible Polymers for Cellular Delivery of Various RNAs.
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-02-24 , DOI: 10.1021/acs.biomac.0c00211
Dong-Chu Yang 1 , Alexander C Eldredge 1 , James C Hickey 1 , Hurik Muradyan 1 , Zhibin Guan 1
Affiliation  

RNA-based therapeutics have garnered tremendous attention due to their potential to revolutionize protein replacement therapies, immunotherapy, and treatment of genetic disorders. The lack of safe and efficient RNA delivery methods has significantly hindered the clinical translation and widespread application of RNA-based therapeutics. With differing sizes and structures of therapeutic RNA molecules, a critical challenge of the field is to develop RNA delivery systems that accommodate these variations while retaining high biocompatibility and efficacy. In this study, we developed a series of multivalent peptide-functionalized bioreducible polymers (MPBP) as a safe and efficient delivery vehicle derived from a core polymer backbone for various RNA species. The facile synthesis of MPBPs from a single polymer backbone provides access to numerous polymers with diverse architectures that enable cellular delivery of different RNA cargos. Postfunctionalization with multifunctional peptides enables strong RNA complexation, enhanced cellular uptake, and facilitates endosomal escape of cargo. The high delivery efficiency and low cytotoxicity for various RNA-MPBP nanoparticles in multiple cell lines demonstrates that the MPBP approach is a novel promising vector strategy for future RNA delivery systems.

中文翻译:

用于多种RNA细胞递送的多价肽官能化生物可还原聚合物。

基于RNA的治疗方法因其潜在的革新蛋白替代疗法,免疫疗法和遗传性疾病的治疗方法而备受关注。缺乏安全有效的RNA递送方法已严重阻碍了基于RNA的治疗剂的临床翻译和广泛应用。随着治疗性RNA分子的大小和结构的不同,该领域的关键挑战是开发适应这些变化并保持高生物相容性和功效的RNA递送系统。在这项研究中,我们开发了一系列多价肽官能化的生物可还原聚合物(MPBP),作为源自各种RNA种类的核心聚合物主链的安全有效的递送载体。从单个聚合物主链轻松合成MPBP即可获得具有多种结构的众多聚合物,这些结构可实现不同RNA货物的细胞递送。用多功能肽进行后功能化可实现强大的RNA络合,增强细胞摄取并促进内体货物的逸出。在多种细胞系中对各种RNA-MPBP纳米粒子的高传递效率和低细胞毒性表明,MPBP方法是未来RNA传递系统的一种新颖的有前途的载体策略。
更新日期:2020-02-24
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