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HIV virus, influenza virus, coronavirus, respiratory syncytial virus, Zika virus, Ebola virus, etc.
Moreover, only a very small number of these RNA viruses have DNA intermediates that can be targeted by CRISPR-Cas9, so powerful Cas9 is also difficult to function
On September 15, 2022, Carver Biosciences, a company dedicated to developing new therapies for these deadly RNA viruses, announced the completion of a seed round led by Khosla Ventures
Carver has developed a programmable platform technology based on CRISPR-Cas13 that provides a universal solution
Dr.
The CRISPR-Cas system is known to be a unique immune system of bacteria and archaea used to fight against foreign viruses or plasmids
In February 2013, Feng Zhang's team pioneered the application of the CRISPR-Cas9 system to gene editing
In August 2016, Feng Zhang's team published a paper in the journal Science [1] that for the first time discovered and confirmed that the CRISPR-Cas13 system can bind and "shred" RNA without cutting DNA, this research not only broadens our understanding of the CRISPR-Cas system, but also shows that Cas13 can be used to develop new RNA targeting tools
In April 2018, Cameron Myhrvold, Pardis Sabeti, et al.
In October 2019, Cameron Myhrvold, Pardis Sabeti, and others published a research paper titled "Programmable Inhibition and Detection of RNA Viruses Using Cas13" in the journal Molecular Cell
The study combined the antiviral activity of Cas13 with its diagnostic capabilities to establish a powerful and rapidly programmable diagnostic and antiviral system, CARVER, that detects and destroys RNA viruses in human cells and could one day be used to diagnose and treat viral infections, including those caused by emerging viruses
CARVER, Cas13-assisted restriction of viral expression and readout, and CARVER also means
This study is the first to use Cas13 for antiviral studies
In this paper, in order to explore new antiviral strategies, the research team focused on Cas13, which can be programmed to target specific sequences of RNA, has few limitations, and is relatively easy to enter cells, and Cas13 has been fully studied
The research team first screened a series of RNA viruses and then looked for viral RNA sequences
The team tested Cas13's activity in human cells infected with three different RNA viruses: lymphocytic choroid plexus meningitis virus (LCMV), influenza A virus (IAV), and herpetic stomatitis virus (VSV
The team further investigated the effect of Cas13 on viral infectivity, and the data showed that after 8 hours of virus exposure, Cas13 reduced the infectivity of the influenza virus to less than three hundredths of the original one
.
At this stage, Carver is using Cas13 to target viruses that infect the respiratory tract (such as influenza viruses and coronaviruses)
at the RNA level.
The goal is to eliminate these viruses and stop them from replicating in humans, and Carver has developed antiviral therapies that can be treated in synergy with vaccinations or antiviral inhibitors to stop the progression
of viral infections.
Carver's modular antiviral system consists of three parts – the delivery system, Cas13 and the guide RNA, the delivery system is lipid nanoparticles or polymer nanoparticles, Cas13 is used to degrade the viral RNA, and the guide RNA is responsible for identifying and targeting the RNA-specific sequence
of the virus.
Original Source:
1.
https://www.
science.
org/doi/10.
1126/science.
aaf5573
2.
https://www.
science.
org/doi/10.
1126/science.
aas8836
3.
https://doi.
org/10.
1016/j.
molcel.
2019.
09.
013
4.
https://www.
carver.
bio/