The "Trojan horse" model-delivery of anti-HBV small interfering RNAs by a recombinant HBV vector.
Hepatitis B virus (HBV) is a small virus that infects the liver. The major obstacle in applying the RNA interference method as an anti-HBV weapon is the challenge to deliver the small interfering RNA molecules to the liver efficiently and specifically. Here we show that HBV-specific short hairpin RNAs (shRNAs) are efficiently expressed from a recombinant HBV into which an shRNA-expressing cassette was inserted, resulting in a significant knock-down of HBV gene expression. Notably, this recombinant HBV still expresses the HBV Core protein, which is targeted by the shRNAs produced by the same vector. Our results set the stage for further use of this recombinant HBV virus with the potential to function as a "Trojan horse"; one that specifically targets the liver and uses the resident virus as an helper for its own propagation, and at the same time eliminate itself and the resident HBV by knocking-down their gene expression.
Shlomai
Amir
A
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. amirsh@tasmc.health.gov.il
Lubelsky
Yoav
Y
Har-Noy
Ofir
O
Shaul
Yosef
Y
D002460:Cell Line; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006509:Hepatitis B / Q000628:therapy; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*
D006512:Hepatitis B Core Antigens; D034741:RNA, Small Interfering