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Synthesis of siRNA Polyplexes Adopting a Combination of RAFT Polymerization and Thiol-ene Chemistry
David
Valade A B,
Cyrille
Boyer A,
Thomas P.
Davis A C,
Volga
Bulmus B C
A
Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
B
School of Biotechnology and Biomolecular Sciences (BABS), The University of New South Wales, Sydney, NSW 2052, Australia.
C
Corresponding authors. Email: t.davis@unsw.edu.au; vbulmus@unsw.edu.au
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Australian Journal of Chemistry 62(10) 1344–1350 http://dx.doi.org/10.1071/CH09208
Submitted: 10 April 2009
Accepted: 24 June 2009
Published online: 13 October 2009
Abstract
Block copolymers of allyl methacrylate and N-(2-hydroxypropyl)methacrylamide (HPMA) with different block lengths have been synthesized by reversible addition–fragmentation chain transfer polymerization. Allyl groups were modified with cysteamine, via a thiol-ene photoreaction, with a high efficiency (~100%) as evidenced by NMR spectroscopy, yielding cationic copolymers of HPMA. Polyelectrolyte complexes of small interfering RNAs (siRNA) and the cationic block copolymers were then formed at an N/P ratio between 1 and 4 depending on the block length of the copolymers. Increasing the length of the hydrophilic block was found to decrease the efficiency of siRNA complexation. The hydrodynamic diameter of the polyplexes in 130 mM buffer solution was less than 100 nm.
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