CRISPR-CAS9 gene-editing tool causes a big challenge to be used in humans for the fear of “scissoring” unintended off-target mutations in the genome. Natural CAS-9 is able to cut genes even when it is not needed. A way to prevent the unintended targeted DNA to be cut, UC Berkeley presented the idea of circular permutation. Circular permutation involves the rearrangements of proteins sequence, connecting the ends with a peptide linker, and cutting the sequence. By making the linker shorter this makes the CAS-9 inactive, which introduced site specific proteases called PROCAS9. ProCas9 has location specifity and is made to exist only in specific organs and tissues. ProCas9 can only be activated when they are cleaved by matching proteases, which means they can respond to specific type of cells. In the study, ProCas9 that are paired with RNA can detect viral proteases and start a defense against flaviviruses by creating DNA damage and terminating the host cells that were infected.
Since CRISPR has been such a big part in science there is worry on how this can potentially damage us in the future. One of these worries pertain to accidentally “scissoring” an unintended targeted DNA. I believe that the site specific ProCas9 is another step forward in making CRISPR a safe and effective use in the future. Also, with more improvements with CRISPR it can be eventually be used in research for its effect on diseases.