Scientists at Salk Institute for Biological Studies have developed a new
version of CRISPR-Cas9 genome editing technology that enabled them to
activate genes without creating breaks in the DNA. This breakthrough has the
potential to help human disease treatment using gene editing tools.
With the original CRISPR-Cas9 system, the process entails use of Cas9 enzyme
together with guide RNAs that target the location where double strand breaks
will be created. Recently, some scientists used a "dead" version of Cas9
which targets specific locations in the genome but no longer cuts the DNA.
Instead, the dCas9 comes with molecular switches that turn on targeted
genes. However, the dCas9 and its switches are too big to fit in the viruses
used to deliver them into cells of living organisms.
Izpisua Belmonte and his team from Salk combined Cas9/dCas9 with various
activator switches to search for a combination that worked even when the
proteins were not fused to one another. Then, they packaged the Cas9 or
sCas9 into one virus, and the switches and guide RNAs into another virus. As
a proof of concept, they used their new approach to treat succesfully
several diseases, including diabetes, acute kidney disease, and muscular
dystrophy, in mouse models.