Between Ebola that kills and the flu that knocks us down, there is one thing in common: both diseases, like many others, are caused by an RNA virus. This type of virus is the cause of the world's most common but deadly diseases. Those against which doctors are often helpless due to the lack of effective treatments. A team of researchers at MIT seems to have found a solution by transforming CRISPR-the famous molecular tool that corrects or precisely cuts letters in the genetic code-into a veritable war machine to kill viruses.
A large number of human pathogens are RNA viruses: Ebola, Zika, or the simple flu are viral diseases and most of them have no effective treatment. This is why the information released this Thursday, October 10 is important. Researchers from the Broad Institute at Harvard's MIT led by Professor Pardis Sabeti announced in the journal Molecular Cell have successfully adapted the Cas-13 enzyme for use as a detector and killer of viruses present in human cells.
Using the power of CRISPR
For several years now, people have been ecstatic or worried about the power of CRISPR, the molecular scissors system capable of correcting a cell's genetic code.
Researchers at the Broad Institute have developed a system called CARVER, an acronym of Cas13-Assisted Restriction of Viral Expression and Readout. It uses the enzyme CRISPR-Cas13 which "naturally targets viral RNA in bacteria," according to a Broad Institute press release.
The team first analyzed RNA viruses to look for viral RNA sequences that Cas13 could target. Their goal at this stage was to cut sequences that were not likely to cause mutations, but which would likely inactivate the virus. « Theoretically, you could program Cas13 to attack virtually any part of a virus "said one of the members of the research team, Cameron Myhrvold in the press release. « But there is great diversity within and between species, and much of the genome changes rapidly as a virus evolves. If you're not careful, you could be chasing a target that ultimately has no effect. It's a reminder of the complexity of the subject and the race that doctors have always been forced to wage with mutant viruses," she says. This is particularly the case with human influenza, which has, over time, taken on various more or less deadly expressions.
Researchers tested the system using human cells infected with three RNA viruses: lymphocytic choriomeningitis virus, influenza A virus and vesicular stomatitis virus. The result is astounding: within 24 hours, the Cas13 enzymes they had previously injected into the cells reduce viral RNA levels by up to 40 times.
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The team then studied the effect of Cas13 on the infectivity of the virus - in other words, how much of the remaining virus could actually continue to infect human cells. The data indicated that eight hours after viral exposure, Cas13 had reduced the infectivity of the influenza virus by more than 300 times!
Not content with this first victory, they then combined their Cas13 system with a diagnostic tool called SHERLOCK. This tool, also created at the Brad Institute and published in Science in February 2018, is a tool derived from the CRISPR technology that allows a number of diagnostic tasks such as the identification of cancer mutations or the detection of viruses using genetic samples. SHERLOCK thus provides the ability to measure viral RNA levels in a sample - and, combined with the Cas13 enzyme attack, gives rise to the CARVER system.
By combining the antiviral activity of Cas13 and the diagnostic capability of SHERLOCK, the research team of Iranian-American geneticist Pardis Sabeti have created a unique system that can one day be used to both diagnose and treat viral infection, including infections caused by new and emerging viruses. This is important because " Human viral pathogens are extremely diverse and constantly adapting to their environment, even within a single virus species, underscoring both the challenge and the need for flexible antiviral platforms. ' John Hultquist, director of intelligence analysis for the cybersecurity company FireEye, explained Forgive Sabeti. « Our work, he continued, establishes CARVER as a powerful and rapidly programmable antivirus and diagnostic technology for a wide variety of these viruses. "
It's an emergency.
This promise is to be welcomed, all the more so as it is urgent. Indeed, over the last 50 years, clinically approved antiviral drugs have been produced. But they treat only nine diseases, a figure that is constantly changing as viral pathogens have the unfortunate tendency to rapidly develop resistance to treatment.
" We envision Cas13 as a research tool to explore many aspects of viral biology in human cells. ' John Hultquist, director of intelligence analysis for the cybersecurity company FireEye, states the geneticist Catherine Freije who participated in the research. « It could also be a clinical tool where these systems could be used to diagnose a sample, treat a viral infection and measure the effectiveness of treatment, while allowing CARVER to be quickly adapted to deal with new or drug-resistant viruses as they emerge. ». A fine hope that must be forged as these viruses wreak havoc on the human population and spread in an uncontrollable manner most of the time.
Source: Freije CA, Myhrvold C, et al. Programmable inhibition and detection of RNA viruses using Cas13. Molecular Cell. Online October 10, 2019. DOI: 10.1016/j.molcel.2019.09.013