RNA therapeutics: Beyond RNA interference and antisense oligonucleotides

Kole, R., Krainer, A. R., Altman, S. (February 2012) RNA therapeutics: Beyond RNA interference and antisense oligonucleotides. Nature Reviews Drug Discovery, 11 (2). pp. 125-140. ISSN 14741776 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22262036
DOI: 10.1038/nrd3625

Abstract

Here, we discuss three RNA-based therapeutic technologies exploiting various oligonucleotides that bind to RNA by base pairing in a sequence-specific manner yet have different mechanisms of action and effects. RNA interference and antisense oligonucleotides downregulate gene expression by inducing enzyme-dependent degradation of targeted mRNA. Steric-blocking oligonucleotides block the access of cellular machinery to pre-mRNA and mRNA without degrading the RNA. Through this mechanism, steric-blocking oligonucleotides can redirect alternative splicing, repair defective RNA, restore protein production or downregulate gene expression. Moreover, they can be extensively chemically modified to acquire more drug-like properties. The ability of RNA-blocking oligonucleotides to restore gene function makes them best suited for the treatment of genetic disorders. Positive results from clinical trials for the treatment of Duchenne muscular dystrophy show that this technology is close to achieving its clinical potential. © 2012 Macmillan Publishers Limited. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: 2' o methoxyethyl phosphorothioate oligonucleotide 2' o methyl phosphorothioate oligonucleotide aln vsp 02 antisense oligonucleotide aptamer avi 5225 custirsen docetaxel double stranded RNA drisapersen eteplirsen fomivirsen gapmer antisense oligonucleotide hybrid antisense oligonucleotide messenger RNA mipomersen morpholino oligonucleotide oblimersen oligonucleotide phosphorothioate placebo RNA induced silencing complex small interfering RNA splice switching oligonucleotide translation suppressing oligonucleotide unclassified drug advanced cancer alanine aminotransferase blood level alternative RNA splicing amino acid sequence antiangiogenic activity antibacterial activity antiviral activity base pairing Becker muscular dystrophy beta thalassemia blocking factor cell activity chemical modification clinical effectiveness clinical trial (topic) congenital pachyonychia Cytomegalovirus retinitis disease course down regulation drug accumulation drug binding drug bioavailability drug blood level drug degradation drug delivery system drug distribution drug efficacy drug fever drug formulation drug half life drug indication drug megadose drug penetration drug safety drug stability drug targeting drug tolerability drug uptake Duchenne muscular dystrophy enzyme activation enzyme activity enzyme degradation gene deletion gene disruption gene expression regulation gene function gene silencing gene therapy genetic disorder human injection site reaction innate immunity low drug dose monotherapy myotonic dystrophy nonhuman overall survival physical chemistry priority journal prostate cancer protein synthesis protein targeting proteinuria respiratory syncytial virus infection retina macula degeneration review RNA binding RNA cleavage RNA degradation RNA interference RNA repair RNA structure side effect single drug dose spinal muscular atrophy treatment duration treatment outcome tumor growth unspecified side effect
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > design
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > design > nucleic acid design > RNAI Design
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > antisense
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > oligonucleotide
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: February 2012
Date Deposited: 30 Jan 2013 19:52
Last Modified: 30 Jan 2013 19:52
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26979

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