Related Experiment Videos
Control of alternative splicing by antisense oligonucleotides as a potential chemotherapy: effects on gene expression
Danielle R Mercatante1, Ryszard Kole
1Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Abstract:
Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of various diseases including cancer. The use of antisense oligonucleotides to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. However, to utilize antisense oligonucleotides as molecular chemotherapeutic agents, the global effects of these molecules need to be examined. The advent of gene expression array technology has now made it possible to simultaneously examine changes that occur in the expression levels of several thousand genes in response to antisense treatment. This analysis should help in the development of more specific and efficacious antisense oligonucleotides as molecular therapeutics.
Insights
Alternative splicing generates mRNA variants crucial for genome function. Antisense oligonucleotides offer novel therapeutic strategies for diseases linked to aberrant splicing, but their global effects require thorough investigation using gene expression arrays.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Alternative splicing of mRNA variants contributes to human genome's functional diversity.
- Aberrant alternative splicing is implicated in disease development, progression, and maintenance, including cancer.
- Antisense oligonucleotides (ASOs) represent a novel therapeutic approach to modulate aberrant splicing patterns.
Purpose of the Study:
- To investigate the global effects of antisense oligonucleotides (ASOs) on gene expression.
- To assess the potential of ASOs as molecular chemotherapeutic agents.
- To guide the development of more specific and efficacious ASO therapeutics.
Main Methods:
- Utilizing gene expression array technology to analyze global gene expression changes.
- Examining the impact of antisense treatment on thousands of genes simultaneously.
- Assessing alterations in alternatively spliced mRNA variant expression levels.
Main Results:
- Gene expression array technology enables simultaneous examination of numerous genes post-antisense treatment.
- This technology facilitates a comprehensive understanding of ASO's molecular effects.
- The analysis provides insights into the global impact of ASO on gene expression profiles.
Conclusions:
- Understanding the global effects of ASOs is crucial for their therapeutic application.
- Gene expression arrays are powerful tools for evaluating ASO efficacy and specificity.
- This approach aids in the development of targeted antisense oligonucleotide therapies for diseases driven by aberrant splicing.