How Editing RNA—Not DNA—Could Cure Disease in the Future

By Kristen V Brown on at

DNA is the code of life, and so advances that allow us to edit that code have unlocked vast potential, from simply editing away the buggy code of disease, to engineering animals that don’t spread illness, to, maybe one day in a distant future, creating so-called designer babies. But editing another essential molecular component of our biology—RNA, the messenger used by cells to turns DNA instructions into proteins—also holds great promise.

A slew of recent high-profile discoveries have focused on pairing the buzzy genetic engineering tool, CRISPR, with RNA editing. RNA is a sort of middleman that turns genetic instructions from DNA into proteins. Editing RNA could allow scientists to tweak how genes are expressed without making permanent changes to the genome itself—thus avoiding one of the scarier aspects of genetic engineering, because you’d be interfering with DNA’s instructions rather than editing DNA itself. RNA is ephemeral, which means changes to it could be reversed. And in some diseases, like a form of muscular dystrophy called myotonic dystrophy, mutant RNA is actually the root of the problem.

In October, scientists at Harvard and MIT’s Broad Institute unveiled, with ample fanfare, a method of editing RNA using the CRISPR system and a protein named Cas13 rather than the usual enzyme CRISPR is paired with, Cas9.

Today, scientists at the Salk Institute published a study in the journal Cell in which they expanded upon RNA editing abilities with the used of a new family of CRISPR enzymes. They dubbed this new system CasRx.

“RNA ‘messages’ are key mediators of many biological processes,” Patrick Hsu, a lead author on the study, told Gizmodo. “In many diseases these RNA messages are out of balance, so the ability to target them directly will be a great complement to DNA editing.”

One of the key features of the new system is that it relies on an enzyme that is physically smaller than those used in previous work. That matters, because it makes it easier for the editing tools to physically make their way into cells to edit them.

“Previously identified Cas13 enzymes are relatively large proteins, thus making it difficult to package for delivery to target tissues,” Hiroshi Nishimasu, a University of Tokyo scientist who was not affiliated with the study, told Gizmodo. “In this study, [researchers] discovered a compact Cas13d enzyme, CasRx. I think that CasRx is a very useful tool from basic research to therapeutic applications.”

In the study, researchers demonstrated the ability to use their new RNA editing system to correct a particular stage in RNA’s process, called splicing, in cells modelled to reflect frontotemporal dementia.

Hsu said his team had specifically been searching for smaller CRISPR enzymes that could facilitated editing neurons and other cell types of the brain. And they wanted something that would be more specific than RNA interference, in which drugs are used to alter RNA’s function.

“Looking forward, this tool will be very useful for studying RNA biology in the near term and hopefully for treating RNA-related diseases in the future,” he said. “Gene editing leads to changes in a genome sequence through DNA cuts, and its effects are permanent in an edited cell. While it is good at turning genes off completely, it’s not so great at tuning a gene’s output more sensitively.”


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