Abstract
The SiRNA strategy is a potent and versatile method for modulating expression of any gene in various species for investigational or therapeutic purposes. Clinical translation of SiRNA-based approaches proved challenging, mainly due to the difficulty of targeted SiRNA delivery into cells of interest and the immunogenic side effects of oligonucleotide reagents. However, the intrinsic sensitivity of immune cells to nucleic acids can be utilized for the delivery of SiRNAs designed for the purpose of cancer immunotherapy. We have demonstrated that synthetic ligands for the intracellular receptor TLR9 can serve as targeting moiety for cell-specific delivery of SiRNAs. Chemically synthesized CpG-SiRNA conjugates are quickly internalized by TLR9-positive cells in the absence of transfection reagents, inducing target gene silencing. The CpG-SiRNA strategy allows for effective targeting of TLR9-positive cells in vivo after local or systemic administration of these oligonucleotides into mice.
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Acknowledgments
This work was supported by the Department of Defense grant number W81XWH-12-1-0132, Prostate Cancer Foundation, STOP CANCER Allison Tovo-Dwyer Memorial Career Development Award and by the National Cancer Institute of the National Institutes of Health under grant numbers R01CA155367 (to M.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Hossain, D.M.S., Moreira, D., Zhang, Q., Nechaev, S., Swiderski, P., Kortylewski, M. (2016). TLR9-Targeted SiRNA Delivery In Vivo. In: Shum, K., Rossi, J. (eds) SiRNA Delivery Methods. Methods in Molecular Biology, vol 1364. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3112-5_15
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DOI: https://doi.org/10.1007/978-1-4939-3112-5_15
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3111-8
Online ISBN: 978-1-4939-3112-5
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