Written byFeng Zhang, Biochemist with the Broad Institute of MIT and Harvard
CRISPR, a naturally occurring system that microbes use to fend off viruses, has been adapted for use as a molecular technology, most notably as a genome editing tool.
CRISPR-based technologies consist of a Cas enzyme, which can cut DNA or RNA (or sometimes both) and a short RNA molecule that directs the Cas enzyme to specific targets by base-pairing with the complementary sequence on the target DNA or RNA.
CRISPR can be reprogrammed to target nearly any site in the genome by giving it the complementary guide RNA. This reprogrammability opens myriad new possibilities for molecular biology and therapeutics. For example, Cas could be directed to a specific disease-causing mutation in a patient’s genome, and once that site of DNA has been cut, a new, healthy version of the gene can be inserted.
CRISPR, however, can be deployed in a number of other ways that can also contribute to improving human health. Here I highlight three ways that CRISPR is being used to combat the global COVID-19 pandemic.
First, CRISPR is being used as a research tool by scientists who are working to better understand how SARS-CoV-2 enters human cells and learn more about the biology of its pathogenesis.
Because CRISPR can be easily reprogrammed, CRISPR-based screening, a method that explores how the loss or gain of each gene in the genome impacts a specific phenotype, has become a powerful tool to learn which genes a viral pathogen relies on for infectivity, an important first step in finding drugs that can block these pathways.
Researchers are also using CRISPR to rapidly test hypotheses about how SARS-CoV-2 works at the molecular level in human cells, such as how an individual human gene is involved. These types of experiments have been greatly accelerated by CRISPR-based tools, leading to an agile research response to this novel threat to human health.
Second, scientists are working to harness CRISPR’s natural viral-defense properties to develop a novel antiviral effective against COVID19.
CRISPR-Cas13, which is a type of CRISPR system that targets RNA, rather than DNA, is being engineered to attack SARS-CoV-2 in patients. By using a guide RNA that matches to a highly conserved region of the SARS-CoV-2 genome, Cas13 can be directed to cut and destroy the virus. Moreover, by taking advantage of the ease of reprogramming CRISPR, multiple guide RNAs can be used to ensure that even if the virus mutates, Cas13 will still recognize it.
This approach can be extended to develop antivirals for related viruses as well, which will enable a rapid response to future pandemics caused by novel pathogens for which we currently have no effective pharmaceutical interventions. One challenge in this area is delivering Cas13 into the most-highly affected cell types, such as lung tissue.
Third, CRISPR is being leveraged to aid in efforts to develop new diagnostic tests to detect the SARS-CoV-2 viral genome in patient samples.
CRISPR-based diagnostics were developed several years ago, and they offer a promising combination of speed and specificity. Over the past few months, these platforms have been adapted to detect COVID19.
One key advantage of some of these CRISPR-based diagnostic platforms is the simplicity of the test assay: they have only a few steps and do not rely on specialized or expensive laboratory equipment.
These features make these tests prime candidates for further development as point-of-care diagnostics that can be deployed in low-resource settings.
The broad availability of inexpensive, easy-to-use tests for COVID19 will dramatically aid in the global fight against this pandemic.