Development of adenovirus vector lacking VA RNA genes for efficient microRNA expression

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Non-coding small RNAs are involved in tumorigenesis. Although the transfection system is used to examine the role of small RNAs, it is not applicable for in vivo studies. Adenovirus vector (AdV) is used to deliver small RNAs including short-hairpin RNA (shRNA) and microRNA (miRNA). However, this vector expresses virus-associated RNAs (VA RNAs). Since VA RNAs are processed using the same pathway as shRNAs, a question arises as to whether VA RNAs influence the RNAi strategy when this vector is used. It has not been tested because VA-deleted AdVs have been difficult to develop.We established a method for VA-deleted AdV production. We compared the activities of shRNAs against hepatitis C Virus (HCV) expressed from VA-deleted AdVs with conventional AdVs. The VA-deleted AdVs inhibited HCV production much more efficiently. Therefore, VA-deleted AdVs were more effective than the current AdVs for shRNA downregulation, probably because of no competition between VA RNAs and the shRNAs.