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Antisense and the kidney
R Oberbauer1, H Murer, G F Schreiner
1Department of Medicine, University of Vienna, Austria.
Abstract:
Antisense oligonucleotides are being used as gene-therapeutic agents. This short overview focuses on the in vivo kinetics and on potential in vivo applications for research purposes as well as therapeutic applications. The most promising experimental results have been obtained with oligonucleotides targeted against genes involved in cell proliferation, such as c-myc, c-myb, Kras, and cdc-2. High parenteral doses of such oligonucleotides have limited growth of experimental tumors, and local application of such oligonucleotides has limited neointimal proliferation in injured arteries. Therapeutic use of antisense in the kidney seems more distant. Because proximal tubule cells take up circulating oligonucleotides, transient suppression of proximal tubule message expression may be obtained following parenteral oligonucleotide administration. More sophisticated delivery systems, however, will be required to achieve antisense efficacy over longer periods and in other compartments of the kidney.
Insights
Antisense oligonucleotides show promise for gene therapy, effectively limiting tumor growth and arterial neointimal proliferation in vivo. Further research into delivery systems is needed for sustained therapeutic effects, particularly in kidney applications.
Area of Science:
- Molecular Biology
- Gene Therapy
- Pharmacology
Background:
- Antisense oligonucleotides (ASOs) are emerging as potent gene-therapeutic agents.
- Understanding their in vivo kinetics and applications is crucial for therapeutic development.
Purpose of the Study:
- To review the in vivo kinetics of antisense oligonucleotides.
- To explore their current and potential research and therapeutic applications.
Main Methods:
- Review of experimental data on antisense oligonucleotide efficacy.
- Focus on in vivo studies targeting specific genes and cellular processes.
Main Results:
- Promising results with ASOs targeting cell proliferation genes (c-myc, c-myb, Kras, cdc-2).
- Demonstrated limitation of experimental tumor growth and arterial neointimal proliferation.
- Transient gene suppression observed in kidney proximal tubule cells after parenteral administration.
Conclusions:
- ASOs show significant potential for treating proliferative diseases.
- Advanced delivery systems are necessary for enhanced and sustained therapeutic efficacy, especially in complex organs like the kidney.