Technique for Correcting Molecular Defects

A study has shown that it is possible to correct defective molecular splicing pathways that would otherwise contribute to cancer and genetic diseases. The study was published in the December 20, 2002, issue of the Journal of Biological Chemistry.

Researchers made these corrections by inserting short strands of genetic material that target portions of RNA into the cell of antisense oligonucleotides. RNA carries the DNA blueprint for cellular protein production in gene expression. The technique was pioneered by Dr. Ryszard Kole, professor of pharmacology at the School of Medicine at the University of North Carolina at Chapel Hill (USA). Dr. Kole and colleagues used the technique to eradicate certain cancer cells to increase their sensitivity to treatment.

Tumors frequently become resistant when cancer cells no long respond to signaling molecules that cause apoptosis. In the study, RNA splicing of the bcl-x gene that controls apoptosis was targeted with antisense oligonucleotides. These antisense molecules were used to shift the alternative splicing of the gene from the anti-apoptotic form to the pro-apoptotic form in cancer cell lines. In so doing, the researchers were able to sensitize these cell lines to various chemotherapeutic agents and radiation.

"This approach could offer a significant advantage over conventional therapies, which are nonspecific and kill both cancerous and noncancerous cells,” said Dr. Danielle Mercatante, first author of the study and a postdoctoral fellow at UNC Comprehensive Cancer Center.




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Univ.of North Carolina School of Med