Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing.
An estimated 60% of all human genes undergo alternative splicing, a highly regulated process that produces splice variants with different functions. Such variants have been linked to a variety of cancers, and genetic diseases such as thalassemia and cystic fibrosis. This Perspective describes a promising approach to RNA repair based on the use of antisense oligonucleotides to modulate alternative splicing and engender the production of therapeutic gene products.
Sazani
Peter
P
University of North Carolina, Lineberger Comprehensive Cancer Center, CB #7295, Chapel Hill, North Carolina 27599-7295, USA.
Kole
Ryszard
R
D017398:Alternative Splicing; D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D016189:Dystrophin / Q000235:genetics; D005914:Globins / Q000235:genetics; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008957:Models, Genetic; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D007690:Polycystic Kidney Diseases / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053649:Receptors, Interleukin-5; D051020:bcl-X Protein; D016875:tau Proteins / Q000235:genetics
D000954:Antigens, Surface; C494811:BCL2L1 protein, human; C505032:CFTR protein, human; D016189:Dystrophin; C546279:GABRG2 protein, human; D008024:Ligands; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D051020:bcl-X Protein; D016875:tau Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005914:Globins; D011972:Receptor, Insulin; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II