Epstein-Barr Virus Cut Out Of Infected Human Cells By CRISPR-Cas9 Genome Editing
Researchers at Stanford exploited the newly developed precision gene editing technology known CRISPR-Cas9 into an anti-virus technology by cutting out Epstein-Barr virus from the host genome of infected cells. Infected cells successfully treated this way scale back proliferation caused by viral programs and engage in a self-destruct program known as “apoptosis”, or controlled cell death. EBV is known to express a “brake” protein that suppresses apoptosis, a way to evade natural defense mechanisms. The researchers also show importantly that there was no toxic effect on non-infected cells.
Epstein-Barr virus (EBV) is most often associated with mononucleosis but is also a cause of more serious conditions such as Burkitt’s lymphoma, nasopharyngeal cancer, and even autoimmune diseases. No therapy exists but the CRISPR-Cas9 study is a valuable avenue as it overcomes two challenges posed by the virus.
The first challenge is during the latent stage of its life cycle it integrates into the genome and exhibits few targets for intervention. In fact most therapeutics under development are focused on attacking the virus during its active “lytic” stage so are not expected to work for cells with virus in latent stage. In the latent stage the virus is still “on”, running a latency program that prompts the cell to proliferate.
The second challenge is that the virus encodes and expresses with the help of the host cell a “brake” protein BHRF1that stops the self-destruct signal stimulated by immune cells in effort to rid the body of cells that have become compromised. The “brake” signal is one reason why EBV is frequently found in cancers: under normal conditions cells that start off on the path to cancer by acquiring mutations get stopped by the cell’s natural ability to undergo “programmed cell death” but EBV halts this process.
The technology for CRISPR-Cas9 entails two parts. The first is the “cutting” enzyme, which is able to cut out pieces of viral DNA that has integrated into the host genome. The second is a “guide RNA” which is a nucleic acid template that matches the desired target, in this case parts of the EBV sequence. The researchers designed a CRISPR-Cas9 system that targets EBV based on its sequence in computer databases.
Once the cells were treated the researches found that latently infected cells no longer proliferated. To ensure that this was not a toxic effect of treatment, the same CRISPR-Cas9 system was applied to cells that lack EBV, in which case there was no effect on proliferation. This is an important point as some criticize CRISPR-Cas9 for its off-target effects in which unintentional cutting occurs.
Source: www.neomatica.com
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