Abstract
Post-transcriptional gene silencing by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis of mammalian cells. Delivery of siRNA into mammalian cells is usually achieved via the transfection of double-stranded oligonucleotides or plasmids encoding RNA polymerase III promoter-driven small hairpin RNA. Recently, retroviral vectors have been used for siRNA delivery, which overcome the problem of poor transfection efficiency seen with the plasmid-based systems. However, retroviral vectors have several limitations, such as the need for active cell division for gene transduction, oncogenic potential, low titers and gene silencing. In this report, we have adapted a commercially available adenoassociated virus (AAV) vector for siRNA delivery into mammalian cells. We demonstrate the ability of this modified vector to deliver efficiently siRNA into HeLa S3 cells and downregulate p53 and caspase 8 expression. Our results suggest that AAV-based vectors are efficient vectors for the delivery of siRNA into mammalian cells. Based on the known ability of these vectors to infect both dividing and nondividing cells, their use as a therapeutic tool for the delivery of siRNA deserves further study.
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References
Barton GM and Medzhitov R . (2002). Proc. Natl. Acad. Sci. USA, 99, 14943–14945.
Brummelkamp T, Bernards R and Agami R . (2002). Cancer Cell., 2, 243.
Brummelkamp TR, Bernards R and Agami R . (2002). Science, 296, 550–553.
Devroe E and Silver PA . (2002). BMC Biotechnol., 2, 15.
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K and Tuschl T . (2001). Nature, 411, 494–498.
Hamilton AJ and Baulcombe DC . (1999). Science, 286, 950–952.
Hammond SM, Bernstein E, Beach D and Hannon GJ . (2000). Nature, 404, 293–296.
Lee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, Salvaterra P and Rossi J . (2002). Nat. Biotechnol., 20, 500–505.
Manche L, Green SR, Schmedt C and Mathews MB . (1992). Mol and Cell. Biol., 12, 5238–5248.
Miyagishi M and Taira K . (2002). Nat. Biotechnol., 20, 497–500.
Paddison PJ, Caudy AA and Hannon GJ . (2002). Proc. Natl. Acad. Sci. USA, 99, 1443–1448.
Paul CP, Good PO, Winer I and Engelke DR . (2002). Nat. Biotechnol., 20, 505–508.
Sharp PA . (1999). Genes and Dev., 13, 139–141.
Sharp PA . (2001). Genes and Dev., 15, 485–490.
Stark GR, Kerr IM, Williams BR, Silverman RH and Schreiber RD . (1998). Ann. Rev. Biochem., 67, 227–264.
Stilwell JL and Samulski RJ . (2003). Biotechniques, 34, 148–150, 152, 154 passim.
Sui G, Soohoo C, Affar el B, Gay F, Shi Y and Forrester WC . (2002). Proc. Natl. Acad. Sci. USA, 99, 5515–5520.
Acknowledgements
We thank Carolyn Pierce and Alejandra Herrera for preparation of figures. This work was supported in parts by grants from the Nearburg Family Foundation, Children Cancer Fund and a Specialized Program of Research Excellence (SPORE) grant, P50-CA70907 from the NIH.
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Tomar, R., Matta, H. & Chaudhary, P. Use of adeno-associated viral vector for delivery of small interfering RNA. Oncogene 22, 5712–5715 (2003). https://doi.org/10.1038/sj.onc.1206733
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DOI: https://doi.org/10.1038/sj.onc.1206733
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