Engineering biodegradable and multifunctional peptide-based polymers for gene delivery

Journal of Biological Engineering

Suzie H Pun¹  Joan G Schellinger¹  Julie Shi¹ 

[1] Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA

关键词: N-(2-hydroxypropyl)methacrylamide (HPMA);    Degradability;    Endosomal escape;    Peptide-polymers;    Nonviral gene delivery;   

Others  :  805198
DOI  :  10.1186/1754-1611-7-25

 received in 2013-08-23, accepted in 2013-10-17,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Shi et al.; licensee BioMed Central Ltd.

【 图 表 】

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