Modification of Alternative Splicing by Antisense Oligonucleotides as a Potential Chemotherapy for Cancer and Other Diseases

Authors: Mercatante D.R.; Sazani P.; Kole R.

Source: Current Cancer Drug Targets, Volume 1, Number 3, November 2001 , pp. 211-230(20)

Publisher: Bentham Science Publishers

Abstract:

It has been estimated that greater than 35percent 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.

Keywords: Antisense Oligonucleotides; Cancer; Beta-thalassemia; Cystic fibrosis; Muscular dystrophy; Fibroblast growth factor receptor; Wilms tumor suppressor; Breast cancer susceptibility genes; Cd44; Xpg

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009013334124

Publication date: 2001-11-01

• Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
  Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
  As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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• In this Subject: Oncology ,  Pharmacology
• By this author: Mercatante D.R. ;  Sazani P. ;  Kole R.

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