Making antisense of splicing.
Alternative splicing multiplies the coding capacity of the genome, resulting in an expanded proteome that provides many targets for therapy. In addition to creating this diverse pharmacoproteome, the process of splicing can be targeted by conventional and molecular therapies. Splicing as a therapeutic target is highlighted in this review, with a particular emphasis on oligonucleotide-based molecular approaches. These oligonucleotides can be used to promote skipping of constitutive exons, inhibit inappropriately activated exons, or stimulate exons weakened by mutations. Preliminary, but exciting, results suggest that these reagents could have clinical utility in treating previously intractable conditions.
Garcia-Blanco
Mariano A
MA
Duke University Medical Center, Department of Molecular Genetics and Microbiology, Center for RNA Biology, Durham, NC 27710, USA. garci001@mc.duke.edu
D017398:Alternative Splicing; D016189:Dystrophin / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000628:therapy; D006801:Humans; D009154:Mutation; D009841:Oligonucleotides / Q000235:genetics / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D012322:RNA Precursors / Q000187:drug effects; D022821:RNA Splice Sites; D012326:RNA Splicing; D012333:RNA, Messenger / Q000187:drug effects; D013873:Thionucleotides / Q000235:genetics
D016189:Dystrophin; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D012322:RNA Precursors; D022821:RNA Splice Sites; D012333:RNA, Messenger; D013873:Thionucleotides