A single genetic mutation can have profound consequences, as demonstrated in neurodegenerative diseases such as amyotrophic lateral sclerosis or Huntington’s disease. A new study by University of Illinois Urbana-Champaign researchers used a targeted CRISPR technique in the central nervous systems of mice to turn off production of mutant proteins that can cause ALS and Huntington’s disease.
Rather than the popular DNA-editing CRISPR-Cas9 technique, the new approach uses CRISPR-Cas13, which can target mRNA – the messenger molecule that carries protein blueprints transcribed from DNA. The Illinois team developed Cas13 systems to target and cut RNAs that code for mutant proteins that trigger ALS and Huntington’s disease, effectively silencing the mutant genes without disturbing the cell’s DNA, said study leader Thomas Gaj, an Illinois professor of bioengineering. The team published its results in the journal Science Advances.
“Targeting RNA rather than DNA has some unique advantages, including the fact that, in theory, its effects within a cell can be reversed since RNAs are transient molecules,” said Colin Lim, a graduate student who helped lead the study. “Because Cas13 enzymes just target RNA, they also carry minimal risk for introducing any permanent off-target mutations to DNA.”