Scientist in the Spotlight:
The Art of Editing RNA
The editing of messenger RNA, or microRNA, is very different than the editing that takes place with CRISPR-Cas9. The former edits the message; the latter edits the DNA. This holds promise in modulating biological processes to treat disease—without altering the DNA blueprint.
Joanne Van Zuidam, Editor of Drug Discovery & Development, a sister publication to LabOutlook,
spoke with Arthur A. Levin, Executive Vice President at Avidity Biosciences. Levin is a pioneer in
oligonucleotide therapeutics and the evolution of RNA therapeutics, including a new editing platform
from the Netherlands-based biotech company ProQR called Axiomer Technology, which can make
single nucleotide changes to RNA in a highly specific and targeted way.
Q: What are the advances in our under- standing of RNA’s role in biology?
A: The science of RNA has come a long way from the original central dogma of
DNA-RNA- protein. We learned in biology class
that the purpose of DNA was to be copied into
messenger RNA and then messenger RNAs were
translated into proteins. What we’ve learned in
the intervening years was that this was a gross
simplification. DNA still holds all of the blueprints
for all of the information in a cell and in an organ-
ism, but it turns out that a large fraction of that
DNA is transcribed and only a small fraction of
the transcribed RNA actually encodes for protein.
That discovery has opened up a whole new
way of thinking about RNA as a therapeutic.
Originally we thought if we can target the messenger RNA we can prevent disease-related
proteins to be expressed. That was the basis for
siRNA and antisense therapeutics. You’d make
an siRNA or antisense drug that inhibited the
messenger RNA from being translated into a
We now know that there are other regulatory
aspects of RNA and we can more broadly affect
biological processes by affecting those regulato-
ry functions. That opens up a whole new realm:
Can we modulate some of the RNA modulators
to modulate downstream effects? That’s a lot of
modulations in a single sentence but it basically
tells us that the level of complexity of RNA is
much greater than just being the recipe for a
protein. If you can modulate the accelerator or
the brake that’s on the particular expression of a
disease-related gene or a family of genes related
to disease you can have much broader effects.
Q: How is the field evolving?
A: You might transcribe a specific sequence of RNA but now we’re learning that there
are enzymes that can make changes to that RNA
Arthur A. Levin, Executive Vice
President, Avidity Biosciences
IN THE SPOTLIGHT