Targeted delivery of siRNA using glycopolymer
S R Simon Ting1*, Eun Hee Min1, Hung T Nguyen1, Martina H Stenzel2, Gyorgy Hutvagner1
1
Centre for Health Technologies (CHT), University of Technology Sydney (UTS), Ultimo NSW 2007, Australia.
2
Centre for Advanced Macromolecular Design (CAMD), University of New South Wales (UNSW), Sydney
NSW 2052, Australia.
Liver is an essential part of the human biological system as it serves to detoxify, synthesize protein and
produce biochemicals necessary for digestion. However, there have been common liver diseases namely,
hepatitis (A, B, C, and E), fatty liver, cirrhosis and ultimately liver cancer. RNA interference (RNAi) mediated
through double-stranded small interfering RNA (siRNA) pave the way to knockdown disease causing gene.1
Nevertheless, effective delivery of siRNA is an arduous task as they are very prone to degradation and are
difficult to target specific cells.
Figure 1. Synthesis of Galactosylated polymers
1.0
3.4% conv.
7.8% conv.
16.2% conv.
0.8
W(Log M) (a.u.)
Glycopolymers are carbohydrates based polymers that
recognise biological receptors on cells.2 This project focuses
on the design of synthetic glycopolymer architectures using
reversible
addition-fragmentation
transfer
(RAFT)
polymerization of sugar containing monomers for
conjugations of siRNA. Galactose based monomer are
selected here, as liver cancer cells over-expressed
asialoglycoproteins, which are galactose recognising
receptors. Moreover, synthetic delivery system has been
reported to protect enzymatic degradation of therapeutics
during delivery in the biological enviroment.3 Figure 1
shows the synthetic approach towards glycopolymers for the
conjugation
of
siRNA
by
using
a
4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]
pentanoic
acid
(CPDT)
RAFT
agent,
4,4′-Azobis(4-cyanovaleric
acid)
(ACVA)
initiator
polymerized in dioxane. Figure 2 display the increased in
molecular weights of polymers with increasing monomer
conversions.
43.0% conv.
64.6% conv.
0.6
0.4
0.2
0.0
3.4
3.6
3.8
4.0
4.2
4.4
4.6
4.8
5.0
5.2
Log M / g mol-1
Figure 2. Gel permeation chromatography of
glycopolymers.
1
G. Hutvagner, M. J. Simard, C. C. Mello and P. D. Zamore, PLos Biology, 2004, 4, 1.
S. R. S. Ting, E. H. Min, P. Escale, M. Save, L. Billon and M. H. Stenzel, Macromolecules, 2009, 42, 9422.
3
D. Peer, J. M. Karp, S. Hong, O. C. Farokhzad, R. Margalit and R. Langer, Nat. Rev., 2007, 2, 751.
2
S. R. Simon Ting
Title: Doctor
Affiliation, Country: Centre for Health Technologies, University of Technology Sydney (UTS),
Australia
Phone: +61 2 9514 4507 E-mail: Simon.Ting@uts.edu.au
Personal History:
2010
PhD in Chemical Engineering (Polymer Chemistry), UNSW
2010-2012
Post-doctoral Research Associate, UNSW
Since 2012
Chancellor’s Research Fellow, UTS
Since 2013
NHMRC Early Career Fellow, UTS
Research interests: Reversible deactivation radical polymerisation; functional polymer; nucleic acids delivery;
glycopolymer; mechanical property of polymer