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Title

Rapid Optimization of Gene Delivery by Parallel End-modification of Poly(ß-amino ester)s

Authors
Zugates, Gregory T.
Peng, Weidan
Jhunjhunwala, Siddharth
Huang, Yu-Hung
Langer, Robert A.
Sawicki, Janet G.
Anderson, Daniel
Published in Molecular Therapy. 2007, vol. 15, no. 7, p. 1306-1312
Abstract Poly(ß-amino ester)s are cationic degradable polymers that have significant potential as gene delivery vectors. Here we present a generalized method to modify poly(ß-amino ester)s at the chain ends to improve their delivery performance. End-chain coupling reactions were developed so that polymers could be synthesized and tested in a high-throughput manner, without the need for purification. In this way, many structural variations at the polymer terminus could be rapidly evaluated. End-modification of the terminal amine structure of a previously optimized poly(ß-amino ester), C32, significantly enhanced its in vitro transfection efficiency. In vivo, intraperitoneal (IP) gene delivery using end-modified C32 polymers resulted in expression levels over one order of magnitude higher than unmodified C32 and jet-polyethylenimine (jet-PEI) levels in several abdominal organs. The rapid end-modification strategy presented here has led to the discovery of many effective polymers for gene delivery and may be a useful method to develop and optimize cationic polymers for gene therapy.
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ZUGATES, Gregory T. et al. Rapid Optimization of Gene Delivery by Parallel End-modification of Poly(ß-amino ester)s. In: Molecular Therapy, 2007, vol. 15, n° 7, p. 1306-1312. https://archive-ouverte.unige.ch/unige:7751

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Deposited on : 2010-06-21

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