Nucleic Acids Research Advance Access published online on June 16, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn342
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Survey and Summaries |
Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA
*To whom correspondence should be addressed. Tel: +1 919 966 4383; Fax: +1 919 966 5640; Email: arjay{at}med.unc.edu
Received April 2, 2008. Revised May 9, 2008. Accepted May 12, 2008.
The potential use of antisense and siRNA oligonucleotides as therapeutic agents has elicited a great deal of interest. However, a major issue for oligonucleotide-based therapeutics involves effective intracellular delivery of the active molecules. In this Survey and Summary, we review recent reports on delivery strategies, including conjugates of oligonucleotides with various ligands, as well as use of nanocarrier approaches. These are discussed in the context of intracellular trafficking pathways and issues regarding in vivo biodistribution of molecules and nanoparticles. Molecular-sized chemical conjugates and supramolecular nanocarriers each display advantages and disadvantages in terms of effective and nontoxic delivery. Thus, choice of an optimal delivery modality will likely depend on the therapeutic context.
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