RNA modulation, repair and remodeling by splice switching oligonucleotides.
Targeting splicing by antisense oligonucleotides allows RNA modifications that are not possible with RNA interference or other antisense techniques that destine the RNA for destruction. By changing the ratio of naturally occurring splice variants the expression of mRNA is modulated. By preventing the use of an aberrant splice site created by a mutation and enforcing re-selection of correct splice sites the RNA is repaired. Antisense induced skipping of the exon that carries a nonsense mutation remodels the mRNA and restores the reading frame of the defective protein. All of the above approaches have clinical applications. Modulation of splice variants is particularly important since close to 60% of all genes code for alternatively spliced pre-mRNA.
Kole
Ryszard
R
Department of Pharmacology, Medicine, Curriculum in Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA. kole@med.unc.edu
Williams
Tiffany
T
Cohen
Lisa
L
D017398:Alternative Splicing; D000818:Animals; D018389:Codon, Nonsense; D004260:DNA Repair; D005091:Exons; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012313:RNA / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D051020:bcl-X Protein; D017086:beta-Thalassemia / Q000235:genetics
C494811:BCL2L1 protein, human; D018389:Codon, Nonsense; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D012313:RNA