The most effective gene-editing tool available today is CRISPR-Cas9. Just this year, scientists have successfully used it for a wide variety of experiments, from modifying vegetables to encoding a Gif in bacterial DNA. However, most recently, it was used to remove a genetic disease from a human embryo.
Although extremely powerful, CRISPR-Cas9 does have its limitations; it’d only able to target DNA. Therefore, to extend its capabilities to RNA editing, scientists from the University of California San Diego School of Medicine developed a modification of CRISPR, and they’ve called it RNA-targeting Cas9 (RCas9).
In a study published in Cell, the UCDS team tested their new tool by correcting the kinds of molecular errors that cause people to develop microsatellite repeat expansion diseases, such as hereditary amyotrophic lateral sclerosis (ALS) and Huntington’s disease.
During standard CRISPR-Cas9 gene editing, a “guide” RMA is instructed to deliver a Cas9 enzyme to a specific DNA molecule. However, the scientists from UCSD instructed it to target an RNA molecule instead.
Tests that were conducted in the laboratory showed that RCas9 removed 95% of problem-causing RNA for myotonic dystrophy types 1 and 2, Huntington’s disease, and one type of ALS. This technique also reversed 93% of the dysfunctional RNA targets in the muscle cells of patient with myotonic dystrophy type 1, resulting in healthier cells.
Senior author Gene Yeo, a cellular and molecular medicine professor at UCSD School of Medicine, explained that “this is exciting because we’re not only targeting the root cause of diseases for which there are no current therapies to delay progression, but we’ve re-engineered the CRISPR-Cas9 system in a way that’s feasible to deliver it to specific tissues via a viral vector.
Across the world, an estimated 450,000 people are living with ALS. Roughly 30,000 of these are American, where 5,600 people are diagnosed with the disease each year. However, the exact number of Huntington’s disease cases is as easy to pin down. One estimate suggests that around 30,000 Americans display symptoms of it, while more than 200,000 are at risk.
Regardless of the exact figures, these two neurological diseases clearly affect a large number of people. This prevalence and the absence of a known cure makes the UCSD team’s research all the more relevant. Even more exciting is the fact that some kinds of RNA mutations that this study is targeting are known to cause over 20 other genetic diseases.
However, the researchers are well aware that what they have accomplished so far is just the first step. While RCas9 works in labs, they still have to figure out how it will fare when tested on humans.
Yeo explains that “the main thing we don’t know yet is whether or not the viral vectors that deliver
RCas9 to cells would elicit an immune response. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities, and evaluate long-term exposure.”
Ultimately, while RCas9 couldn’t deliver a cure exactly, it could potentially extend a patient’s life. For diseases such as ALS and Huntington’s, that’s a very good place to start.
Source: futurism
Images: depositphotos
