A New Advancement in CRISPR Genome Editing Achieved by Salk Scientists

The new tool developed by scientists targets RNA to cut and replace disease-causing genes with healthy ones.

CRISPR genome-editing technology is a relatively new discovery, but its phenomenal growth has made it the new face of molecular biology and gene therapy. This revolutionary technology got a powerful push with the discovery of new RNA targeting “molecular scissors”.

The research was carried out by a team of Salk Institute scientists led by Patrick Hsu and included Peter Lotfy, Silvana Konermann, Jennifer Oki, and Nicholas Brideau. The research was published in Cell under the title Transcriptome engineering with RNA-targeting Type VI-D CRISPR effectors.

The therapeutic use of gene editing to cure diseases had been in focus with researchers targeting DNA of the diseased cell. But DNA is only one side of the story. Researchers revealed that in many cases, it is the RNA which is the main culprit.

For example, faulty RNA messages give rise to a protein imbalance, which translates into diseases like spinal muscular atrophy, atypical cystic fibrosis, and frontotemporal dementia (FTD).

CRISPR systems were developed by prokaryotic organisms to fight off viruses and other pathogens. It is used widely by bacteria as an immune response system.

The bacteria remembers a part of the genome of invading pathogen and use it to identify the pathogen on any subsequent attack. It then employs some enzymes to cut-off the identified part of the genome thereby, disabling the attacking pathogen.

Scientists use this system to cultivate programmable enzymes and then edit the genomes as they like.

The idea of the existence of an RNA targeting CRISPR system has been a part of the discussion among molecular biologists for some time. Patrick Hsu, a senior author of the paper, noted that millions of years of evolutionary development suggest that there must be an RNA targeting system somewhere.

From left: Peter Lotfy, Silvana Konermann, Patrick Hsu, Jennifer Oki and Nicholas Brideau
Source: Salk Institute

His team employed computers to search through the available data of genome sequences. Soon, they came across RNA-targeting type VI-D CRISPR-Cas family, which they named Cas13d.

The team, then, developed the programmable ribonuclease CasRx with the help of protein engineering. This success encouraged the researchers to try it out in human cells to modulate RNA messages.

The team decided to test it against the neurodegenerative disease frontotemporal dementia (FTD). The Adeno-associated virus (AAV) delivery of dCasRx to FTD affected neurons effectively fought off Tau is-splicing and restored the healthy level of protein.

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The new discovery is unique in its approach, but this is not the first of its kind. RNA-guided and RNA-targeting methods have been discovered previously by different labs.

However, the CasRx method has some notable improvement which will make it popular in coming times. This new technology is easy to deploy owing to its small size.

It is also very accurate and safer than other technologies.

“Nature is full of so many secrets,” adds Hsu. “It’s really a rich, untapped resource for inventing new technologies.”

With so many different biological and chemical systems in millions of species, we must always be ready for new surprises. The successful implementation of this technology in animals will open new doors for therapeutic advancement.