Volume 2 Supplement 1

2005 International Meeting of The Institute of Human Virology

Open Access

Novel Second Generation Anti-HIV shRNA Expressing vif and Decoy TAR Arrest the Virus-breakthrough Phenomenon Associated With siRNA-escape Variants

  • J Barnor1, 4,
  • N Miyano-Kurosaki1, 2,
  • Y Abumi1,
  • K Yamaguchi1,
  • K Ishikawa3,
  • N Yamamoto3 and
  • H Takaku1, 2Email author
Retrovirology20052(Suppl 1):P36

https://doi.org/10.1186/1742-4690-2-S1-P36

Published: 8 December 2005

We describe a novel chimera RNA expressing vif short-hairpin RNA (shRNA) and decoy trans-activation response region (TAR) RNA from a human U6 Pol II promoter, which enhanced the inhibition of human immunodeficiency virus (HIV) vif small-interfering RNA (siRNA) and arrested virus breakthrough by siRNA-generated escape variants in long-term culture assays. Our strategy was based on a second-generation anti-HIV-1 shRNA vector system, in which HIV-1 vif shRNA was fused to a decoy TAR RNA by a linker UU cleavage site to generate vif shRNA-decoy TAR RNA. Upon expression, the RNA molecule was cleaved and separated into vif siRNA and decoy TAR RNA. The synergistic effect of these molecules enhanced the inhibition of HIV-1 replication in a long-term culture assay and prevented virus breakthrough associated with siRNA-mediated escape variants. Combining shRNA with decoy TAR RNA as second-generation anti-HIV shRNA may provide practical basis for applying siRNA-based gene therapy to the treatment of HIV/AIDS.

Notes

Authors’ Affiliations

(1)
Dept. Life Environ. Sci, Center, Chiba Inst. Tech.
(2)
High Tech. Res. Center, Chiba Inst. Tech.
(3)
NIHDiseases, AIDS Res. Center
(4)
Dept. Virol, Noguchi Memo. Inst. Univ.

Copyright

© The Author(s) 2005

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