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Hot article: RAFT polymer delivers RNA


09 June 2008

Scientists in the US and Australia have used a polymer to deliver short interfering RNA (siRNA) into cells.

The therapeutic affect of RNA interference by specific gene silencing could lead to treatments for and/or prevention of many diseases such as diabetes, hepatitis, AIDS and cancer. However siRNA must be delivered to target sites within the body in order for this treatment to be effective.

Heather Maynard and co-workers at the University of California and Volga Bulmus and colleagues from the University of New South Wales have utilised reversible addition-fragmentation chain transfer (RAFT) polymerisation. This is a controlled polymerisation technique, which Maynard has used to create polymers which can form reversible covalent conjugates with siRNA. The polymer is stable in blood, but once inside a cell the bonds break, releasing the siRNA.

Other living radical polymerisation techniques have previously been used to produce cationic polymers which form non-covalent complexes with siRNA, but this is the first example of a system where covalent bonds hold the polymer and siRNA together.

 

                     Synthetic method for SiRNA-polymer conjugate using RAFT polymerisation

 

The team used poly[poly(ethylene glycol) acrylate] due to its ability to protect the siRNA and and also due to its longer circulation lifetime. A novel chain transfer agent with an activated pyridyl disulphide end-group was designed by the team for its stability and is essential for conjugation to the thiol containing biomolecules.

In the future, Maynard hopes to work towards improving in vivo stability, distribution and biological activity by further developing these polymerisation and conjugation techniques.

'We believe that combining the advantages of controlled radical polymerisations and site specific polymer conjugation with siRNAs in a rational way will lead to improved in vivo applicability of the revolutionary siRNA strategy' said Maynard.

Sylvia Pegg

Link to journal article

Reversible siRNA–polymer conjugates by RAFT polymerization
Karina L. Heredia, Thi H. Nguyen, Chien-Wen Chang, Volga Bulmus, Thomas P. Davis and Heather D. Maynard, Chem. Commun., 2008, 3245
DOI: 10.1039/b804812f