Progress in microRNA delivery
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- 作者：Yu Zhang ; Zaijie Wang ; Richard A. Gemeinhart
- 关键词：AMO ; anti-miRNA oligonucleotides ; APP ; amyloid precursor protein ; BBB ; blood&ndash ; brain barrier ; bp ; base pairs ; CNS ; central nervous system ; CSC ; cancer stem cell ; DDAB ; dimethyldioctadecylammonium bromide ; DGCR8 ; DiGeorge syndrome critical region gene ; DNA ; deoxyribonucleic acid ; DOTMA ; 1 ; 2-Di-O-octadecenyl-3-trimethylammonium propane ; FANA ; fluorine derivatives nucleic acid ; GC4 ; phage identified internalizing scFvs that target tumor sphere cells ; HCV ; hepatitis C virus ; iNOP ; nanotransporte
- 刊名：Journal of Controlled Release
- 出版年：28 December, 2013
- 年：2013
- 卷：172
- 期：3
- 页码：962-974
- 全文大小：1318 K
文摘
MicroRNAs (miRNAs) are non-coding endogenous RNAs that direct post-transcriptional regulation of gene expression by several mechanisms. Activity is primarily through binding to the 3鈥?untranslated regions (UTRs) of messenger RNAs (mRNA) resulting in degradation and translation repression. Unlike other small-RNAs, miRNAs do not require perfect base pairing, and thus, can regulate a network of broad, yet specific, genes. Although we have only just begun to gain insights into the full range of biologic functions of miRNA, their involvement in the onset and progression of disease has generated significant interest for therapeutic development. Mounting evidence suggests that miRNA-based therapies, either restoring or repressing miRNAs expression and activity, hold great promise. However, despite the early promise and exciting potential, critical hurdles often involving delivery of miRNA-targeting agents remain to be overcome before transition to clinical applications. Limitations that may be overcome by delivery include, but are not limited to, poor in vivo stability, inappropriate biodistribution, disruption and saturation of endogenous RNA machinery, and untoward side effects. Both viral vectors and nonviral delivery systems can be developed to circumvent these challenges. Viral vectors are efficient delivery agents but toxicity and immunogenicity limit their clinical usage. Herein, we review the recent advances in the mechanisms and strategies of nonviral miRNA delivery systems and provide a perspective on the future of miRNA-based therapeutics.