Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA.
J Biol Eng. 2013 Oct 24;7(1):25. doi: 10.1186/1754-1611-7-25.
The complex nature of in vivo gene transfer establishes the need for multifunctional delivery vectors capable of meeting these challenges. An additional consideration for clinical translation of synthetic delivery formulations is reproducibility and scale-up of materials. In this review, we summarize our work over the last five years in developing a modular approach for synthesizing peptide-based polymers. In these materials, bioactive peptides that address various barriers to gene delivery are copolymerized with a hydrophilic backbone of N-(2-hydroxypropyl)methacrylamide (HPMA) using reversible-addition fragmentation chain-transfer (RAFT) polymerization. We demonstrate that this synthetic approach results in well-defined, narrowly-disperse polymers with controllable composition and molecular weight. To date, we have investigated the effectiveness of various bioactive peptides for DNA condensation, endosomal escape, cell targeting, and degradability on gene transfer, as well as the impact of multivalency and polymer architecture on peptide bioactivity.
体内基因转移的复杂性确立了对多功能输送载体的需求，这些载体能够满足这些挑战。对于合成输送制剂的临床转化，另一个需要考虑的因素是材料的可重复性和规模化。在这篇综述中，我们总结了过去五年在开发基于肽的聚合物合成方法方面的工作。在这些材料中，通过可逆加成-断裂链转移（RAFT）聚合，将针对基因传递的各种障碍的生物活性肽与 N-(2-羟丙基)甲基丙烯酰胺（HPMA）的亲水性主链共聚。我们证明，这种合成方法可以得到具有可控组成和分子量的、结构明确的、窄分散的聚合物。迄今为止，我们已经研究了各种生物活性肽在 DNA 凝聚、内涵体逃逸、细胞靶向和基因转移的可降解性方面的有效性，以及多价性和聚合物结构对肽生物活性的影响。
