Modification of alternative splicing by antisense oligonucleotides as a potential chemotherapy for cancer and other diseases.
It has been estimated that greater than 35% of all human genes undergo alternative splicing. The process of alternative splicing is highly regulated and disruption of a splicing pattern can produce splice variants that have different functions. Certain splice variants that are associated with induction of cell death, regulation of cellular proliferation and differentiation, cell signaling, and angiogenesis are present in a variety of cancers. Several of these cancer-related alternatively spliced genes will be discussed in this review. In addition, alternative splicing is associated with several genetic disorders such as beta-thalassemia, cystic fibrosis, and muscular dystrophy. Control of pre-mRNA splicing patterns with antisense oligonucleotides presents an attractive way to potentially treat and manage a variety of diseases. This review will discuss potential gene targets for antisense oligonucleotide induced modification of alternative splicing patterns. Furthermore, the chemistries and delivery strategies of antisense oligonucleotides will be discussed.
Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, USA.
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Mercatante
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Sazani
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Kole
D017398:Alternative Splicing / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D015195:Drug Design; D016147:Genes, Tumor Suppressor; D006801:Humans; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D009857:Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics / Q000628:therapy
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger