When the coronavirus pandemic emerged in January, bioengineers at Stanford University were working on a system to fight the flu with the gene-editing technology CRISPR. They immediately focused their attention to using CRISPR for fighting COVID 19 and according to their recent report, they’ve developed a way to inhibit 90% of coronaviruses, including SARS-CoV-2, the cause of COVID-19.
Standford’s Prophylactic antiviral CRISPR
Working with researchers at the Department of Energy’s Lawrence Berkeley National Laboratory, they developed a technique called prophylactic antiviral CRISPR in human cells, or PAC-MAN. The technology disables viruses by scrambling their genetic code. PAC-MAN combines a guide RNA with the virus-killing enzyme Cas13. The RNA directs Cas13 to neutralize and destroy certain nucleotide sequences in the SARS-CoV-2 genome.
To effectively deliver PAC-MAN to the lung where COVID-19 often does the most damage, the Stanford team turned to the Berkeley Lab’s Molecular Foundry, which has been working on lipitoids, a type of synthetic peptide that can deliver DNA and RNA into cells. As a result, they were able to reduce the amount of SARS-CoV-2 virus in solution by more than 90%. They are now planning animal trials with collaborators at New York University and Karolinska Institute in Sweden.
According to Michael Connolly, a principal scientific engineering associate at Berkeley Lab, combining an effective lipitoid delivery with CRISPR targeting could enable a very powerful strategy for fighting viral disease such as COVID-19 as well as against new viral strains with pandemic potential.
CRISPR is already being used in diagnosing COVID-19 by using the enzyme Cas13a to identify an RNA sequence that’s unique to SARS-CoV-2. The CRISPR-based test from Sherlock Biosciences that can diagnose COVID-19 in about an hour has been in use since May 2020.
Aside from using CRISPR to eliminate viruses, researchers are looking into using the gene-editing technology to eliminate HIV, the virus that causes AIDS, as well as for fighting influenza.
CSIC researchers target CRISPR tools to destroy the COVID-19 coronavirus genome
Meanwhile, a team of researchers from the Spanish National Research Council, or the Consejo Superior de Investigaciones Científicas (CSIC), is leading a project to use the CRISPR genetic editing tool with the aim of destroying the RNA genome of the coronavirus SARS-CoV-2, which has caused the Covid-19 pandemic.
Most types of CRISPR tools are capable of cutting DNA through a programmable scissor-like protein called Cas which cuts the genome of any species at specific targets simply by being guided by a small RNA molecule, the intermediary nucleic acid that usually transports the genetic information from the nucleus to the cytoplasm of the cell, where the proteins will be produced.
The lead researcher, geneticist Lluís Montoliu, stated that their project aims to utilize the Cas13d protein that is capable of directly cutting RNA, and not DNA, in a very specific way. If the genome of the SARS-CoV-2 coronavirus which causes COVID-19, is an RNA molecule, programming one of the Cas13d proteins, with a guide of RNA complementary to the coronavirus genome to cut it and destroy the cell.
Together with his team Dolores Rodríguez Aguirre (CNB-CSIC), Miguel Ángel Moreno Mateos (CABD-CSIC-UPO) and Almudena Fernández, CIBER-ISCIII, will be using the CRISPR molecular ‘scissors’ to directly attack the heart of the coronavirus, its RNA genome, to destroy it without disturbing any of the other RNA molecules in the cell, which are necessary for it to continue functioning.
The project will test the functionality and non-toxicity of CRISPR reagents in zebrafish embryos, then they will be tested against RNA viruses and finally, they will be tested against cells infected with the current coronavirus. If the therapeutic strategy is successful, the next step would be to test it on mice.
The project brings together researchers from the CNB-CSIC, the Centro Andaluz de Biología del Desarrollo (CABD-CSIC-UPO) and the CIBER-ISCIII. It is funded by the CSIC through the Global Health Platform.