11th Annual Conference Of The British HIV Association [BHIVA] 20–23 April 2005, Burlington Hotel·Dublin·Ireland

[AUTHOR(S):] M McClure¹, MD Moore¹, MJ McGarvey², RA Russell¹, BR Cullen^3
1Jefferiss Trust Laboratories, Wright-Fleming Institute, Imperial College London, UK, ²Hepatology, QEQM, Imperial College London, UK, ³Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology, Duke University Medical Centre, Durham, USA

BHIVA Conf 2005 Apr 20-23;11:O29

AIM: To investigate the potential of RNA interference (RNAi) for the treatment of Hepatitis B virus (HBV) infection.

METHODS: An RNAi sequence active against the HBV surface antigen (HBsAg) was expressed from a polymerase III expression cassette. Therapeutic use of RNAi demands a suitable delivery system. Hence, the expression cassette was inserted into two vector systems, one based on the Prototype Foamy Virus (PFV), the other, Adeno-Associated Virus (AAV). Both are non-pathogenic and capable of integration into cellular DNA. The vectors containing the HBV targeted RNAi molecule were introduced into a cell line stably expressing HBsAg (293T.HBs) and one which secreted infectious HBV virions (HepG2.2.15).

RESULTS: We identified an RNAi sequence active against HBsAg. Further, we demonstrated knockdown of HBsAg by approximately 90%, compared with controls in 293T.HBs cells transduced by shRNA-encoding PFV and AAV vectors. This reduction has been observed up to 5 months post-transduction in single cell clones. Both vectors successfully inhibited HBsAg expression from HepG2.2.15 cells, even in the presence of HBV replication.

CONCLUSIONS: This work is the first to demonstrate that delivery of RNAi by viral vectors has therapeutic potential for chronic HBV infection and establishes the ground work for the use of such vectors in vivo.

PRESENTING AUTHOR: M McClure

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2005-04-20
O29

Copyright © 2005 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD