Key to curing cancer, HIV, autism found
DUBAI — In a breakthrough research that may lead to cures for for some of the world’s most perplexing diseases, scientists at the University of California, San Diego, were able to target RNA in living cells using the gene-editing technique.
According to a study published in the magazine Cell, researchers have determined how to isolate and edit messenger RNA that carries genetic instructions from the cell’s nucleus to make new proteins for the first time using gene-editing tool Clustered Regularly Interspaced Short Palindromic Repeats, also known as CRISPR-Cas9.
The US News and World Report said the researchers had previously used this tool to remove HIV from human immune cells and shut down HIV replication permanently. CRISPR-Cas9 can also potentially be used to edit genes that determine our physical features and maybe even our personality, lead- ing to ethical questions about how to responsibly use the technology.
The gene- editing technique could lead to treatments for diseases that are linked to defective RNA and have previously been
Gene editing tool can isolate, repair RNA in living cells
untreatable. These include certain cancers, fragile X syndrome and autism.
“This work is the first example, to our knowledge, of targeting RNA in living cells with CRISPRCas9,” said senior author Gene Yeo, PhD, associate professor of cellular and molecular medicine. “Our current work focuses on tracking the movement of RNA inside the cell, but future developments could enable researchers to measure other RNA features or advance therapeutic approaches to correct disease-causing RNA behaviours.”
Reporting the breakthrough, Canada Journal explained that RNA’s location in a cell — and how and when it gets there — can influence whether proteins are produced in the right location and at the appropriate time. For instance, proteins important to neuronal connections in the brain, known as synapses, are produced from RNAs located at these contacts. Defective RNA transport is linked to a host of conditions ranging from autism to cancer and re- searchers need ways to measure RNA movement in order to develop treatments for these conditions.
Efforts to edit and measure DNA got a big boost a few years ago. That’s when researchers discovered they could take CRISPRCas9, a naturally occurring defence mechanism bacteria use to fend off invading bacteria, and apply it to edit genes in mammalian systems, said Canada Journal.
Normally, CRISPR-Cas9 works like this: researchers design a “guide” RNA to match the sequence of a specific target gene. The RNA directs the Cas9 enzyme to the desired spot in the genome, where it cuts the DNA. The cell repairs the DNA break imprecisely, thus inactivating the gene, or researchers replace the section adjacent to the cut with a corrected version of the gene.
Until now, CRISPR-Cas9 could only be used to manipulate DNA. Yeo and colleagues at the University of California applied the technique to develop a flexible means of targeting RNA in live cells, also called RNA-targeted Cas9 (RCas9), said Canada Journal.
In order to target RNA instead of DNA, the researchers altered several features of the CRISPRCas9 system. Building upon previous work by co-author Jennifer Doudna, PhD, at UC Berkeley, they designed a short nucleic acid called the PAMmer that, along with the guide RNA, directs Cas9 to an RNA molecule.
The Canada Journal report said that to test the system, Yeo’s team targeted the RNA that encodes the proteins ACTB, TFRC and CCNA2. Then they watched as Cas9, fused with a fluorescent protein, revealed the movement of RNA into stress granules, a cluster of proteins and RNAs that form in a cell’s cytosol (the area outside the nucleus) when the cell is under stress. Stress granules are linked to neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). This system allowed the team to track RNA over time, in live cells, without the need for artificial tags commonly used in other RNA-tracking techniques — an approach that can interfere with normal cellular processes.