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Nucleic Acids Res. 2016 Aug 19;44(14):6518-48. doi: 10.1093/nar/gkw236. Epub 2016 Apr 15.

The delivery of therapeutic oligonucleotides.

Author information

1
UNC Eshelman School of Pharmacy and UNC School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA arjay@med.unc.edu.

Abstract

The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology.

PMID:
27084936
PMCID:
PMC5001581
DOI:
10.1093/nar/gkw236
[Indexed for MEDLINE]
Free PMC Article

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