16 | New Scientist | 30 January 2021
A METHOD for altering RNA that
works similarly to the CRISPR
DNA-editing technique has proven
effective in animal tests and could
be a powerful new tool for doctors.
The approach, created by a
team led by Prashant Mali at
the University of California, San
Diego, is inherently safer than
CRISPR because it doesn’t alter
the genome. What’s more, it might
be used to temporarily alter gene
expression, which could treat
conditions such as chronic pain.
“This is a clever and elegant
approach,” says Gaetan Burgio at
the Australian National University
in Canberra. “Overall, I believe this
technique has great potential.”
The recipes for making the
proteins our bodies need are stored
in the DNA inside cells. When we
require proteins, our cells use DNA
to make a complementary single
strand of RNA. This “messenger
RNA”, or mRNA, is then sent to the
cell’s protein-making factories.
These mRNA strands aren’t
simple copies of the recipes, or
genes. They can get changed in
many ways before being used as
protein templates. Cells havecomplex RNA-editing systems,
which do everything from cutting
out the junk in our genes that gets
transferred to RNA to changing
the sequence itself.
Sometimes, two parts of a single
RNA piece can bind to form a
double strand. When this happens,
so-called ADAR enzymes in our
cells recognise the double-stranded
section and edit the sequence by
effectively changing the letter Ain the RNA code to a G at specific
sites. Exactly why is unknown.
These bits of double-stranded
RNA can be created artificially by
adding “antisense RNAs”, which
are pieces of RNA whose sequence
is complementary to part of a
strand of mRNA. This method has
been used before to edit RNA, but
it doesn’t work well, perhaps
because antisense RNA rapidly
breaks down.
Now, Mali and his colleagues
have tried using circular pieces
of antisense RNA, which are more
stable. This boosted thepercentage of mRNA with the
desired edit around fourfold, to
as high as 90 per cent in human
cells in a dish. The effect also
lasted for several days.
Next, the team used the
approach to treat mice with
the same mutation that causes
Hurler syndrome in people. This
mutation disables an enzyme,
leading to a build-up of harmful
sugars. Mali’s team managed to
correct up to 20 per cent of the
mutant RNA in the mice’s livers,
halving the sugar build-up
(bioRxiv, doi.org/frvt).
For this experiment, a virus
was used to deliver DNA coding
for the antisense RNA to the
cells. Although the DNA wasn’t
integrated into the genome, this
means the effect lasts indefinitely.
But antisense RNAs could also be
delivered in fatty droplets, as is
done in some of the new covid-
mRNA vaccines, in which case the
effects would last only weeks.
This approach is limited to
changing an A to a G in the RNA
code. But it might be possible to
develop similar approaches that
SC would enable a C to U change. ❚
IENCE
PHOT
O^ LIBRAR
Y/ALA
MYNews
RNA, as illustrated here,
acts as a messenger from
DNA for making proteinsAnimal behaviourA MATHEMATICAL solution to a
biological puzzle that might not
actually exist could prove useful
in the design of hopping rovers
for space exploration.
Alberto Vailati at the University
of Milan, Italy, normally researches
the physics of fluid dynamics. But
he was intrigued to read some lab
studies in which insects, including
fruit fly larvae and froghoppers, had
been seen leaping with an averagetake-off angle of about 60 degrees.
The idea that many types of
insects should have independently
evolved to leap at this angle seemed
odd to Vailati: a 45-degree take-off
angle is the natural choice, as this
maximises the range of a jump.
Recently, one of his students,
Samuele Spini, suggested an
explanation: a 60-degree take-off
angle may help the insects avoid
obstacles mid-leap.
Vailati, Spini and their colleagues
then built a mathematical model
to test the idea. They found that
a take-off angle of 60 degrees
minimised the probability of strikingthe side of a step-like or fence-like
obstacle of random size and
position lying ahead (arxiv.org/
abs/2101.05133).
There is a hitch though:
insects may not typically leap at a
60-degree angle. Malcolm Burrows
at the University of Cambridge has
spent much of his career studying
insect neurobiology, including
jumping behaviour, and is unaware
of any research indicating that awide range of insects typically leap
at such a precise and unusual
take-off angle.
The new study might nonetheless
prove useful for engineers who are
designing hopping rovers to explore
astronomical bodies.
Gareth Meirion-Griffith at NASA’s
Jet Propulsion Laboratory in
California is exploring this concept.
He says this derivation of an
optimum take-off angle of
60 degrees could be helpful for
exploration robots jumping in
places with very rough surfaces
and low gravitational pull. ❚MedicineMichael Le PageTime for RNA editing
Altering RNA rather than DNA could be a safer approach for medicine
Physicists work
out the best way
for insects to jump“A take-off angle of
60 degrees minimises
the probability of striking
an obstacle lying ahead” Joe Paul