AIDS Treatment: RNA with a homing warhead
AIDS can be cured genetically
Alla Solodova, Infox.ru
Pharmacologists have created and tested a genetic cure for HIV: the virus did not die, but stopped multiplying.
AIDS patients are killed even by "native" conditionally pathogenic organisms - those that are present in a healthy human microflora. Scientists have not yet defeated HIV due to the high variability (mutagenicity) of the viral genetic material. However, pharmacologists have learned to pacify the virus with the help of highly active antiretroviral therapy (VAART). With regular medication and proper nutrition, infected people do not lose their working capacity and can fully live for about ten years. However, VAART loses its effectiveness during treatment – the patient develops resistance to drugs. And the side effects of therapy are not the most pleasant: from uneven obesity (too thin legs and thick stomach and neck) and diarrhea to damage to internal organs and the nervous system.
Contraceptive for HIVVadim Pokrovsky, head of the Federal AIDS Center, explained to the correspondent Infox.ru that VAART drugs inhibit enzymes or block the process of virus-cell fusion.
But HIV gets used to therapy too quickly. Moreover, the virus is embedded in human DNA and after a while begins to multiply again. Therefore, pharmacologists and virologists want to supplement or completely replace VAART drugs with a class of compounds that can stop the reproduction of the virus at the genetic level. That is, scientists plan to sterilize the virus and in this way almost completely get rid of it.
Researchers from the USA led by Charles Preston Neff from the University of Colorado (Colorado State University) have created and tested the desired molecule. Scientists did not make any discovery, but simply gathered together the available knowledge.
It is known that small interfering RNAs (siRNAs) suppress the expression of viral genes. They "stick" to the main or matrix RNA of the virus and in this way do not allow the encoded information to become a protein reality. However, in previous experiments, siRNA molecules failed to "reach" the immunodeficiency virus, and they did not penetrate the protein envelope (capsid).
But in the arsenal of biologists there are small sequences of nucleic acids that perform the functions of highly specific receptors of organic compounds – aptamers. Once in the cell, they affect only one target protein. And if an aptamer to one of the viral proteins is introduced into the cell, then only HIV, and not the whole cell, will feel the "blow".
Charles Preston Nef and his colleagues synthesized siRNA, which blocks the expression of genes responsible for the reproduction of the virus. Then they created a hybrid of the "contraceptive" siRNA and an aptamer to the viral protein Bal. We can say that scientists have attached a "homing warhead" to the antiviral molecule, which detects HIV and drags the "viral contraceptive" through the protein envelope.
Human miceThe effectiveness of the molecular hybrid was tested by biologists in in vitro experiments and on transgenic mice with human immunity (genotype RAG-hu).
That is, virologists studied the effectiveness of the drug in relation to human, not monkey immunodeficiency. Biologists treated animals with a hybrid and separate components – aptamer and siRNA. The scientists compared the results with the control – uninfected animals and infected, but not receiving treatment.
It turned out that the hybrid molecule inhibits the immunodeficiency virus better than others. Depending on the intensity of therapy, the normal level of lymphocytes (immune cells that die due to HIV) was maintained for 3-9 weeks. The concentration of viral RNA in the blood decreased to an undetectable level for more than three weeks.
Scientists note that the hybrid non-toxic molecule also causes mutations in the virus: HIV is trying to adapt to the drug. However, there is not a single dominant mutation among the mutations. This means that the virus will not be able to learn to ignore treatment too quickly.
"The molecule is not toxic, but it has to pass more than one test. We hope that patients with resistance or painful sensitivity to HAART will have a chance not to die in the coming years," the scientists write in the article An Aptamer–siRNA Chimera Suppresses HIV-1 Viral Loads and Protects from Helper CD4+ T Cell Decline in Humanized Mice.
"The described technique is progressive and promising. I think that in this way it will be possible to drive the virus into a corner and not get AIDS at all," Vadim Pokrovsky rejoiced at the success of his American colleagues, "Russian researchers from the Central Institute of Epidemiology are also working on genetic methods to combat HIV."
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24.01.2011