Abstract
Once considered genetic “oddities”, microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms—ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles—are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.
Keywords: AntimiR, cancer therapy, chemical modification, microRNA inhibition, liposome, polymer nanoparticle, oligonucleotide, oncomiR, antisense therapeutics, tumor targeting.
Current Medicinal Chemistry
Title:Canonical and Non-Canonical Barriers Facing AntimiR Cancer Therapeutics
Volume: 20 Issue: 29
Author(s): Christopher J. Cheng, W. Mark Saltzman and Frank J. Slack
Affiliation:
Keywords: AntimiR, cancer therapy, chemical modification, microRNA inhibition, liposome, polymer nanoparticle, oligonucleotide, oncomiR, antisense therapeutics, tumor targeting.
Abstract: Once considered genetic “oddities”, microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms—ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles—are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.
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Cite this article as:
Cheng J. Christopher, Saltzman Mark W. and Slack J. Frank, Canonical and Non-Canonical Barriers Facing AntimiR Cancer Therapeutics, Current Medicinal Chemistry 2013; 20 (29) . https://dx.doi.org/10.2174/0929867311320290004
DOI https://dx.doi.org/10.2174/0929867311320290004 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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