Adenoviral Vectors as Versatile Tools for miRNA Delivery and | 91139
International Research Journals

Adenoviral Vectors as Versatile Tools for miRNA Delivery and Expression


Mohammad Khalid Parvez*

Only 20 years after the discovery of miRNAs, rapid progress has been made in understanding the functional impact of deregulated miRNAs on disease development, especially cancer. These observations and functional studies form the basis for the development of miRNA-based diagnostic markers or new therapeutic strategies. Adenoviral (Ad) vectors are one of the most commonly used vector types in gene therapy and are suitable for high-level, short-term transgene expression in a variety of cells. Here we report the setup and functionality of an Ad-based miRNA vector platform that can be deployed to efficiently deliver and express high levels of miRNAs. This vector platform enables rapid and efficient production of high-titer vectors and expression of pri-miRNA precursors under the control of the polymerase II promoter. Unlike non-viral miRNA delivery systems, this Adbased miRNA vector platform enables precise dosing of the delivered miRNA. Using a two-vector model, we have shown that Ad-driven miRNA expression is sufficient to downregulate the expression of overexpressed and highly stable proteins. Additional data confirmed the downregulation of several endogenous target RNAs using the system presented here. Furthermore, we report some unexpected synergistic effects on transduction efficiency in vitro when cells are sequentially transduced with two different Ad vectors. This effect is possible in protocols that use two or more different Ad vectors simultaneously.

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