Gene therapy against HIV
Japanese scientists have applied the method of genomic editing to inactivate the human immunodeficiency virus
Marina Astvatsaturyan, Echo of Moscow
Having destroyed the regulatory genes of the virus that causes AIDS through the CRISPR/Cas9 genomic editing system, a group of researchers from Kobe University has blocked the reproduction of particles by HIV-infected cells. This is reported by an article in Scientific Reports (Ophinni et al., CRISPR/Cas9 system targeting regulatory genes of HIV-1 inhibits viral replication in infected T-cell cultures).
The defeat of the human immunodeficiency virus (HIV-1) is a chronic disease that has been diagnosed in more than 35 million people worldwide. The level of infection can be controlled with antiretroviral drugs, but there is no complete cure.
One of the main problems is the inability to remove cells with latent, not yet manifested HIV infection: as the virus multiplies, its genes are inserted into the chromosomes of infected cells and reproduced together with the genetic material of the cell, for the time being, without giving themselves away.
The recently used CRISPR/Cas9 genomic editing system seems to Japanese scientists to be a promising tool for inactivating HIV genes embedded in the chromosomes of people affected by this virus: it cuts genes in certain places, which allows you to remove or add sections of DNA.
Researchers from Kobe targeted two genes that regulate the reproduction of HIV, these genes are called tat and rev. Based on the genetic information about the six main subtypes of the human immunodeficiency virus, they constructed six types of guide RNA, which ensures the specificity of editing by the CRISPR/Cas9 system.
Then the scientists created a vector – a special design based on a special virus with a long incubation period, a lentivirus carrying the genes of the Cas9 cutting enzyme and a guide RNA. When introducing such a vector with an editing system into the culture of cells that produced products of the tat and rev genes, the authors achieved a significant decrease in the activity of target genes, and, accordingly, the level of their products.
No side, undesirable mutations were observed, as well as changes in the survival rate of cultured cells. By introducing an editing system into the culture of cells with latent or permanent HIV infection, the authors noticeably suppressed HIV reactivation dependent on cytokine immune system proteins, as well as the reproduction of viral material in chronically infected cells. Moreover, the simultaneous introduction of all six types of RNA-conductor almost completely blocked the production of the virus by infected cells.
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