Synthesis of siRNA Polyplexes Adopting a Combination of RAFT Polymerization and Thiol-ene Chemistry

David Valade; Cyrille Boyer; Thomas P. Davis; Volga Bulmus

doi:10.1071/CH09208

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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 and Volga Bulmus ^B ^C

+ Author Affiliations

- Author Affiliations

^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

Australian Journal of Chemistry 62(10) 1344-1350 https://doi.org/10.1071/CH09208
Submitted: 10 April 2009 Accepted: 24 June 2009 Published: 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.

Acknowledgements

V.B. and T.P.D. acknowledge the receipt of Discovery Grants from the Australian Research Council (ARC). T.P.D. is also thankful for a Federation Fellowship from the ARC.

References

Synthesis of siRNA Polyplexes Adopting a Combination of RAFT Polymerization and Thiol-ene Chemistry

Abstract

Acknowledgements

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