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Polymer siRNA conjugates synthesised by controlled radical polymerisation
Authors:Vanessa Loczenski Rose  G Sebastiaan Winkler  Stephanie Allen  Sanyogitta Puri  Giuseppe Mantovani
Institution:1. School of Pharmacy, Boots Science Building, University Park, University of Nottingham, Nottingham NG7 2RD, UK;2. Astrazeneca UK Ltd., Pharmaceutical Development, Alderley Park, Macclesfield SK10 2NA, UK
Abstract:Oligonucleotide therapeutics such as antisense RNA, micro RNA, mRNA and small interfering RNA have great potential to generate a novel therapeutic portfolio within the pharmaceutical market. The promising outlook of oligonucleotide therapeutics lies in their ability to knockdown genes responsible for disease progression. However, the efficient delivery of RNA medicines without causing toxicity remains a major challenge. With growing interest in siRNA therapeutics, a number of synthetic polymers have been developed to facilitate efficient in vitro and in vivo delivery. With the advent of controlled radical polymerisation (CRP) techniques – such as RAFT polymerisation and ATRP – new families of well-defined polymers with narrow molecular weight distribution and predictable molecular architecture potentially suitable to generate siRNA delivery devices are becoming available. In this review article we will describe and discuss how CRP can be utilised to generate siRNA delivery nanodevices.
Keywords:Controlled radical polymerisation  RAFT  ATRP  siRNA  RNA interference  Gene delivery
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