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Hepatocyte-specific delivery of small inhibitory RNA (siRNA) for treatment of viral hepatitis

Reference	BBS/B/03599
Principal Investigator / Supervisor	Professor Leonard Seymour
Co-Investigators / Co-Supervisors	Professor Jon Preece
Institution	University of Oxford
Department	Oncology
Funding type	Research
Value (£)	246,541
Status	Completed
Type	Research Grant
Start date	01/05/2004
End date	30/04/2007
Duration	36 months

Abstract

Small inhibitory RNA (siRNA) is capable of specific down regulation of hepatitis B and C proteins, but cannot be delivered to hepatocytes in vivo. Here we will use polyelectrolyte complexes based on siRNA condensed with pH-responsive cationic polymers containing reducible disulphides and terminated with thiolated ligands. These vectors should be capable of receptor-specific delivery, combining endosomolytic activity (via the proton sponge effect) with efficient reduction-triggered intracytoplasmic unpackaging and release of siRNA. An important challenge of the project will be to enable sufficient serum stability to allow access to hepatocyte receptors, and this will be addressed by template-assisted condensation of siRNA using reducible cationic polymers that can be subsequently crosslinked via reducible disulphides for efficient intracytoplasmic activation.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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