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Gene therapy of AIDS

Specialists of the V.A. Engelgardt Institute of Molecular Biology, Russian Academy of Sciences, and the “Vector” Main Research Center of Virology and Biotechnology created and tested on the cell culture three genetic structures capable to suppress reproduction of human immunodeficiency virus (HIV-1) in human cells.

At present, the virus is fought against by chemical agents. The drugs subscribed to the patients act predominantly on key HIV-1 enzymes - reverse transcriptase, invertase and protease. There are a lot of antiviral drugs, but they are often ineffective as HIV mutates quickly and acquires drug resistance. And these drugs are, one should note, toxic and very expensive.

Meanwhile, the human organism’s cells possess powerful natural mechanism which should regulate the work of genes including viral ones. It is called RNA-interference. In an extremely simplified form, RNA-interference is damage to a certain RNA sequence with participation of a different, “defending” RNA molecule. This system prevents viral infection, unless viruses had learned to cut it off in the course of evolution. Researchers from countries including Russia are developing the artificial RNA-interference system. It is non-injurious to the patient and, due to high specificity of action, does not damage its own RNA in cells infected by the virus.

To fight against HIV, Russian biologists have created three genetic structures. These structures contain short nucleotide sequences that find the most conservative molecules among all RNA molecules, that is, sequences that do not change quickly and are important to the virus. These sequences are then “damaged”. The structure also includes the gene of green fluorescent protein, which allows to determine is the gene structure has entered the cell or not.

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The researchers embedded the gene structures created by them into cultivated lymphoid cells. Cells which have been penetrated by the fluorescent protein begin to glow with green. Within 24 and 72 hours after introduction of genetic structures, the cells were infected by human immunodeficiency virus (GKV-4046 culture), and several days later the researchers assessed the degree of viral welfare by specific antigen accumulation. It has turned out that the genetic structures significantly suppress viral reproduction.

The extent of damage to viral RNA depends on the viral dose received by the cell itself and on the sequence of the structure per se. The sequence aimed at the reverse transcriptase area of viral genome turned out to be the most efficient, being capable of suppressing the viral production in the cells by 91 to 98 percent within three days.

In the researchers’ opinion, similar genetic structures can be used in AIDS gene therapy. At present, the researchers continue the effort on creation of efficiently operating structures, including the ones that are able to overcome high virus mutation.

Nadezda Markina | alfa
Further information:

Further reports about: RNA sequence structure

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