01 April 2008

RNA interference: caution is needed!

The results obtained by scientists at the University of Kentucky, working under the guidance of Professor Jayakrishna Ambati, call into question some of the mechanisms of action of a new class of drugs designed to block certain genes using RNA interference.

The mechanism of RNA interference, discovered in 1998, already in 2006 brought the authors of the study the Nobel Prize. Initially, scientists identified a class of double-stranded RNAs with pronounced abilities to block gene activity. After that, synthetic versions of such molecules were created – small interfering RNAs (miRNAs), designed to selectively prevent the expression of genes that cause the development of various diseases. This does not lead to irreversible damage to DNA, so the RNA interference method quickly gained popularity in the field of biomedical research and gave rise to a new class of drugs designed to block the synthesis of proteins associated with diseases or replication of viruses penetrating the body.

The authors claim that miRNAs do not have a specific, as previously thought, but rather a systemic effect on the body. Therefore, miRNA-based drugs, some of which are already undergoing clinical trials, may have a serious negative side effect. According to Ambati and his co-authors, the reason lies in the fact that miRNAs do not penetrate into the cell and trigger RNA interference, but, regardless of their sequence and target, bind to the TLR3 cell surface receptor and block the growth of blood vessels in the eyes, skin and other organs. (Toll-like receptors – Toll-like receptors, TLR – localized on various immunocompetent cells, play a key role in the activation of innate immunity.)

Blocking the growth of blood vessels suppresses the development of certain diseases, including macular degeneration and cancer. However, with intravenous administration of miRNA, it can have a detrimental effect on other organs.

The authors have no doubt that RNA interference exists, but they are sure that, contrary to the generally accepted opinion, it is not a mechanism of action of miRNA. They insist that researchers need to study in detail the mechanisms of action of miRNAs and approach clinical trials using miRNA-based drugs with great caution.

In addition, they note the need to study the systemic action of miRNA and the possibilities of using it for the treatment of diseases such as macular degeneration and cancer.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily


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