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Modification of alternative splicing by antisense oligonucleotides as a potential chemotherapy for cancer and other

D R Mercatante1, P Sazani, R Kole

  • 1Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, USA.

Current Cancer Drug Targets
|August 22, 2002
PubMed

Insights

Alternative splicing, a key gene regulation process, generates variants impacting cancer and genetic disorders. Antisense oligonucleotides offer a promising therapeutic strategy by modulating these splicing patterns.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Over 35% of human genes utilize alternative splicing, a crucial regulatory mechanism.
  • Dysregulated splicing patterns yield splice variants with altered functions, implicated in diseases.
  • Aberrant splice variants are linked to cancer, including cell death, proliferation, and angiogenesis.

Purpose of the Study:

  • To review cancer-associated alternatively spliced genes.
  • To explore the role of alternative splicing in genetic disorders like beta-thalassemia, cystic fibrosis, and muscular dystrophy.
  • To discuss antisense oligonucleotides (ASOs) as a therapeutic approach for modulating alternative splicing.

Main Methods:

  • Review of literature on alternative splicing in cancer and genetic diseases.
  • Identification of key alternatively spliced genes relevant to disease pathology.
  • Discussion of ASO chemistry and delivery strategies for therapeutic applications.

Main Results:

  • Several cancer-related alternatively spliced genes and their functions are highlighted.
  • The association of alternative splicing with genetic disorders is detailed.
  • Potential gene targets for ASO-based splicing modulation are identified.

Conclusions:

  • Alternative splicing plays a significant role in various cancers and genetic disorders.
  • Antisense oligonucleotides represent a viable therapeutic strategy for correcting aberrant splicing patterns.
  • Further research into ASO chemistries and delivery is essential for clinical translation.

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