There may be a new entrant soon in the competitive race of gene editing: San Diego’s Isis Pharmaceuticals has teamed up with University of California, San Diego to produce research that demonstrates a commercially feasible way to use RNA to deploy CRISPR/Cas9 gene editing system.
It shows in a study published November 16 in Proceedings of the National Academy of Sciences that RNA technology can be used to “turn the CRISPR/Cas9 system on and off as desired, but only temporarily activating CRISPR-Cas9.”
Isis Pharmaceuticals develops RNA-targeted compounds that could create molecules that enhance the CRISPR mechanism – and could do so on an industrial scale, said C. Frank Bennett, senior author on the paper and senior vice president of research at the company.
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There are two important steps in CRISPR technology: Using RNA to locate the sequence of DNA that’s in need of editing, and using a Cas-9 enzyme to snip away that portion of genetic material.
“These findings provide a platform for multiple therapeutic applications, especially for nervous system diseases, using successive application of designer CRISPR RNA drugs,” co-senior author Don Cleveland, Chair of the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine, said in the statement.
The publicly traded Isis Pharmaceuticals has built its repute on RNA-targeted drug development, and has a broad pipeline of antisense drugs – including two that have been commercialized.
Bennett spoke with UT San Diego on Isis Pharmaceuticals’ potential role in developing the first portion of CRISPR technology:
“We thought it would be interesting to determine the potential of our technology for this CRISPR/Cas9 application,” Bennett said. “We mapped out a series of experiments that were the genesis of this paper. It’s part of our having a very good, interactive collaboration. A new idea came forward, and we thought it was interesting enough that we would both put resources on it.”
Unlike antisense, which temporarily inhibits gene activity, CRISPR produces permanent changes in the genome itself, Bennett said. But the role of RNA brings it into familiar Isis territory.
“Surprisingly, this new pathway uses RNA as a central component for developing both for the activation of the (Cas9) enzyme and the specificity of what the enzyme edits,” he said.
Isis applied its ability to chemically modify RNA to improve its activity to the field of CRISPR, and found that the technology also worked there.
The Isis RNA works transiently, then is degraded, Bennett said. That is an advantage because the limited activity decreases the opportunity for off-target effects.
As an aside, the decades-old biotech is considering a name change, given the fraught political climate around the term “Isis.”
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