CRISPR screening for coronavirus is in the works. CRISPR screening helps identify genes that cause diseases such as sickle-cell anemia, cancer, and lung cancer metastasis. The technology enables thousands of genes to be modified, helping scientists identify and assess their function in a single experiment. However, CRISPR screening can only target or edit DNA, which is not useful for RNA viruses such as the flu. Ongoing studies are being undertaken involving CRISPR screening for coronavirus—which contains an RNA genome.
Neville Sanjana, Ph.D. — an Assistant Professor of Biology at New York University and Assistant Professor of Neuroscience and Physiology at NYU School of Medicine as well as a Core Faculty Member at the New York Genome Center—along with other researchers at the New York Genome Center and New York University, have developed a new type of CRISPR screening technology which will target RNA using Cas13 enzymes. This is according to their publication in Nature Biotechnology.
CRISPR Screening for Coronavirus: RNA Focused
According to Sanjana, they will undergo an in-depth study to develop the key principles and predictive modeling to produce the most effective Cas13 screening guide design. CRISPR Cas13 enzymes are capable of target gene knockdown without altering the genome, making them a potentially significant therapeutic for influencing gene expression, thanks to their programmable RNA-guided, RNA-targeting proteins with nuclease activity. This screening technology can be used to understand many aspects of RNA regulation and to identify the function of non-coding RNAs, which are RNA molecules that are produced but do not code for proteins.
Tom Maniatis, Ph.D.—Family Scientific Director and Chief Executive Officer, New York Genome Center—pointed out that advancement in the fields of genomics and precision medicine are the kind of innovation that they foster and develop at the New York Genome Center.
Developing Cas13-Based Tools
Co-first authors of the study—postdoctoral scientist Hans-Hermann Wessels and Ph.D. student Alejandro Méndez-Mancilla—were able to gather information for more than 24,000 RNA-targeting guides by developing a suite of new Cas13-based tools and conducting a transcript tiling and permutation screen in mammalian cells. They were also able to find interesting biological insights that may help in expanding the application of RNA-targeting Cas13 enzymes. These include important regions of the guide RNA useful in recognizing a target. Being able to identify the target region will help scientists design accurate guides vital for screening and therapeutic applications. They are also useful for next-generation biosensors that can more precisely discriminate between closely related RNA species.
The researchers were able to notice a marked difference in protein knockdown when targeting different protein-coding and non-coding elements of messenger RNAs and found evidence that Cas13 competes with other RNA-binding proteins involved in transcript processing and splicing. Méndez-Mancilla also adds that they intend to use the optimized Cas13 screening system to target noncoding RNAs which greatly expands the CRISPR toolbox for future genetic and transcriptomic screens.