New method tracks gene expression in single cells over space and time
Messenger RNA (mRNA) made its big leap into the public limelight during the pandemic, thanks to its cornerstone role in several COVID-19 vaccines. But mRNAs, which are genetic sequences that instruct the body to produce proteins, are also being developed as a new class of drugs. For mRNAs to have broad therapeutic uses, however, the molecules will need to last longer in the body than those that make up the COVID vaccines. 

Researchers from the Broad Institute of MIT and Harvard and MIT have engineered a new mRNA structure by adding multiple “tails” to the molecules that boosted mRNA activity levels in cells by 5 to 20 times. The team also showed that their multi-tailed mRNAs lasted 2 to 3 times longer in animals compared to unmodified mRNA, and when incorporated into a CRISPR gene-editing system, resulted in more efficient gene editing in mice. 

The new mRNAs, reported in Nature Biotechnology, could potentially be used to treat diseases that require long-lasting treatments that edit genes or replace faulty proteins. 

“The use of mRNA in COVID vaccines is fantastic, which prompted us to explore how we could expand the possible therapeutic applications for mRNA,” said Xiao Wang, senior author of the new paper, a core institute member at the Broad and an assistant professor of chemistry at MIT. “We’ve shown that non-natural structures can function so much better than naturally occurring ones. This research has given us a lot of confidence in our ability to modify mRNA molecules chemically and topologically.”

“I’m most excited by the fact that this new shape of mRNA is so well tolerated by cellular translation machinery,” said Hongyu Chen, first author of the paper and a graduate student from MIT Chemistry in Wang’s lab. “This opens up many new opportunities for synthetically modifying mRNA to extend its therapeutic uses.”

Source: https://www.broadinstitute.org/news/messenger-rnas-multiple-tails-could-lead-more-effective-therapeutics