New CRISPR Tool Restores Protein Imbalance in Dementia Patient's Cells

CRISPR experts at Salk Institute for Biological Sciences in the U.S. successfully developed a new tool called CasRx that targets not the DNA, but the RNA, and then used it to correct a protein imbalance in cells from a dementia patient, restoring them to healthy levels. The work is published in Cell journal.

"Bioengineers are like nature's detectives, searching for clues in patterns of DNA to help solve the mysteries of genetic diseases," says Patrick Hsu, a Helmsley-Salk Fellow and senior author of the study. "CRISPR has revolutionized genome engineering, and we wanted to expand the toolbox from DNA to RNA."

CRISPR has been used as a power gene editing tool targeting the DNA. The Salk team searched for bacterial genomes that could target RNA, which could then be designed to fix problems with RNA and resulting proteins. They found a family of CRISPR enzymes that targets the RNA and called it Cas13d. Similar to Cas9 family, Cas13d enzymes coming from various bacterial species also exhibit different activities. They searched to the best version that can be used for human cells, which turned out to be from  Ruminococcus flavefaciens XPD3002. Thus, the tool was named CasRx.

Dementia patients have imbalance of two versions of the tau protein. The team designed the CasRx to target RNA sequences for the version of the tau protein that is overproduced. CasRx was proven to be 80 percent effective in rebalancing the tau protein to healthy levels.

Read more from Salk.