HIV may develop resistance to gene therapy
Genetic therapy was able to create invincible viruses
An international team of scientists from universities in Canada and Japan found out that the CRISPR/Cas9 genome editing system, which is hoped for as a potentially effective way to fight HIV, can make the immunodeficiency virus stronger. The study is published in the journal Cell Reports (Wang et al., CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape).
In order to reproduce, HIV needs to embed its DNA into the genome of an infected cell. Then the cell begins to synthesize the elements of the virus itself, which are collected into new infectious particles. The CRISPR/Cas9 system is able to "spoil" the DNA of the virus by inserting individual extra nucleotides into it, which makes the information about proteins and RNA molecules encrypted in it meaningless. By destroying the "factory" for the production of the immunodeficiency virus with the help of artificial mutations, CRISPR/Cas9 prevents further reproduction of HIV and stops infection.
However, there is a serious flaw in this seemingly flawless approach. Scientists have found that HIV can acquire resistance to the genome editing system, like bacteria adapting to antibiotics. Some of the viruses that survived after CRISPR/Cas9 passed through them are protected from genome rewriting with the help of other mutations.
According to scientists, a paradoxical situation is developing. Mutations that make the virus unable to reproduce can give it protection from genetic "scissors" elsewhere. CRISPR/Cas9 works as follows: RNA molecules recognize a specific section of DNA, and the Cas9 protein secures its cutting. In gene technologies, another DNA fragment is inserted into the incision site, which allows manipulating the genome. However, if the mutation changes this site, then CRISPR/Cas9 will not be able to do anything. Such mutations are a product of the virus' natural selection.
Diagram from the Cell Press HIV can develop resistance to CRISPR/Cas9 – VM press release.
The researchers emphasize that their discovery does not mean that CRISPR/Cas9 will be ineffective in the fight against HIV. The problem lies in the same area as the emergence of antibiotic resistance: drugs were effective at one time, but new microorganisms have emerged that they do not act on. When developing a new genetic therapy, scientists emphasize, it is necessary to take into account possible limitations. For example, use not only the Cas9 enzyme, but also other proteins.
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08.04.2016