Publication date: Feb 06, 2020
In 2012, his team at the University of TcFCbingen in Germany discovered that by linking enzymes to engineered strands of RNA, they could change the sequences of messenger RNA molecules in cells.
RNA editing, by contrast, could allow clinicians to make temporary fixes that eliminate mutations in proteins, halt their production or change the way that they work in specific organs and tissues.
Several hurdles remain: current technologies can alter RNA sequences in only a few limited ways, and getting the system to work as intended in the human body will prove challenging.
Still, researchers hope that new technologies, such as protein engineering, and improved methods for delivering RNA to cells can help to overcome these limitations.
A foundational tenet in molecular genetics-its central dogma-was that cellular machinery faithfully transcribes genetic information from a double-stranded DNA template into a single-stranded RNA messenger, which is then translated into a protein.
Some have speculated that the ADAR proteins evolved as a defence against viruses, but many viruses with double-stranded RNA are unaffected by the enzymes.
It seems that highly intelligent cephalopods, such as squid, cuttlefish and octopuses, use RNA editing extensively to adjust genes involved in nerve-cell development and signal transmission.
No other animals are known to use RNA editing in this way.
A similar fate, he learnt, had befallen the work of researchers at a company called Ribozyme, who in 1995 proposed ‘therapeutic editing’ of mutated RNA sequences by inserting complementary sequences into frog embryos and allowing ADARs to edit the resulting double-stranded molecule and correct the mutation.
Peter Beal, a chemist at the University of California, Davis, says that the 2016 publication of the molecular structure of ADAR bound to double-stranded RNA made the system more understandable and enabled scientists to better engineer the enzyme to enhance its delivery or make it more efficient.
Many see RNA editing as an important alternative to DNA editing using techniques such as CRISPR.
Rosenthal expects, moreover, that RNA editing will prove useful for diseases without a genetic origin.
Permanently changing the Nav1. 7 gene through DNA editing could eliminate the ability to feel pain and disrupt other necessary functions of the protein in the nervous system, but tuning it down through RNA editing in select tissues for a limited amount of time could help to alleviate pain without the risk of dependency or addiction associated with conventional painkillers.
Although the system edited only a small amount of the RNA encoding dystrophin, it restored the protein to about 5% of its normal level in the animals’ muscle tissue, an amount that has shown therapeutic potential.
- Investigating RNA editing in deep transcriptome datasets with REDItools and REDIportal.
- Therapeutic Advances for Huntington’s Disease.