01 July 2008

Reprogrammed poliovirus for safe vaccination

Molecular biologists and computer scientists from Stony Brook University, working under the guidance of Professor Eckard Wimmer, have developed and synthesized a new class of weakened polioviruses. They used special software to methodically recode the genome of the polio virus, after which they demonstrated the possibility of immunizing animals with weakened synthetic versions of the virus. The results obtained give hope for the emergence of a new class of live antiviral vaccines.

Six years ago, Eckard Wimmer and his colleagues synthesized the world's first artificial virus, a wild–type poliovirus. This achievement was a significant step towards the work that scientists are currently engaged in.

Due to the peculiarities of the genetic code, there is an unimaginably large number of possible coding options for any protein. For poliovirus proteins, the number of possible encodings exceeds the number of atoms in the universe. With the help of a powerful computer algorithm, scientists have identified possible variants of gene encoding, presumably weakening the virus.

They introduced hundreds of tiny mutations into the genome of the virus, which exactly preserved the viral proteins, but violated the mechanism of their coding in RNA. At the same time, during the synthesis of the amino acid chain, transport RNAs (tRNAs) were added to the chain of pairs of amino acids that cannot function normally while in neighboring positions. The process of creating such a virus was called SAVE – Synthetic Attenuated Virus Engineering (Creation of a synthetic attenuated virus). As a result of this process, a virus is obtained whose genome encodes completely authentic wild-type virus proteins. However, each of the hundreds of mutations causes a tiny defect in the translation of the genetic code into a protein.

Translation of such an unusual genome into viral proteins is ineffective, so the most heavily recoded virus was weakened to such an extent that it lost the ability to infect cells.

Scientists injected various variants of synthetic poliovirus into mice, most of which did not have any manifestations of the disease, but the synthesis of antibodies against poliovirus took place. These viruses are not yet suitable for human vaccination, but the proposed approach has enormous potential. The authors hope that with its help it will be possible to create weakened versions of a large number of different viruses.

Experts emphasize that for the development of synthetic weakened viruses, it is necessary to use computer algorithms, because only they allow you to simultaneously create a huge number of mutations and, thus, not only weaken the virus, but also exclude the possibility of its return to the wild type.

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


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