Intracellular Delivery of RNA-based Therapeutics Using Aptamers

Abstract

The clinical potential of siRNAs for silencing genes critical to disease progression is clear, but a fail-proof method for delivering siRNAs to the cytoplasm of diseased tissues or cells has yet to be identified. A variety of delivery approaches have been explored to directly or indirectly couple siRNAs to delivery vehicles. This review explores the use of synthetic single-stranded DNA and RNA aptamers as a means to deliver siRNAs, shRNAs and antisense oligonucleotides for therapeutic intervention. Topics covered include: the advantages and challenges of using aptamers as delivery tools; current aptamer-mediated siRNA delivery platforms for the treatment of cancer and HIV; and emerging methodologies for the identification of aptamers capable of internalizing into target cell types.

Acknowledgements

We thank James O McNamara II for useful discussions and careful review of the manuscript.

Financial & competing interests disclosure

Kristina W Thiel acknowledges a Ladies Auxiliary to the Veterans of Foreign Wars Postdoctoral Fellowship. Paloma H Giangrande acknowledges support from the NIH (1RO1 CA138503-01A1, 1R21DE019953-01), and the Mary Kay Ash Foundation (MKACF 001-09). Paloma H Giangrande is a co-inventor on patent application PCT/US2007/012927_DELIVERY METHOD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.