-- All You Need to Know About The Latest Gene
Editing Breakthrough
Reproductive biologist Shoukhrat Mitalipov
led a team of scientists from Oregon Health
& Science University, Portland, and the Salk
Institute, California, as well as collaborators
in South Korea and China, to make a pretty
huge breakthrough in gene editing.
They targeted a dangerous mutation in a gene
which makes seemingly healthy adults prone
to sudden and fatal heart attacks. Using their
technique, they were able to get rid of the
mutation in embryos that would’ve gone on
to become a baby that would’ve grown up
without the disease.
So, thanks to Mitalipov & co., it would now
seem that we are closer to a future where
disease-causing mutations in genes can be
corrected to ensure healthy babies. As if
the nature of his research wasn’t newsworthy
enough, there was a further flutter of excitement
thanks to a mysterious leak.
-- What was the leak?
Mitalipov’s paper was due to be published
in Nature journal on August 2 (until the date
and time of publishing, studies are under
strict embargo). But somehow, parts of the
media caught wind of it almost a week earlier
(examples here and here).
There is still no clarity on how this happened.
The jury is also out on what the implications
of such high profile leaks in scientific research
are.
-- What is the gene that was edited?
The gene is called MYBPC3. We all have two
copies of it in each of our cells. It plays
a major role in maintaining the structure
and function of the heart. About 1 in 500
(0.2%) of us inherits a mutation in one of
our MYBPC3 genes.
This makes us susceptible to a condition called
hypertrophic cardiomyopathy (HCM). It manifests
in young, otherwise healthy, carriers in the
form of sudden heart attacks.
In fact, HCM is known as the most common form
of sudden death among young athletes and is
even more alarmingly common among Indians.
Some studies say that more than 4% of Indians
carry this mutation.
A parent who is a carrier of a mutated gene
has a 50% chance of passing the defect down
to his or her offspring – provided the other
parent’s gene does not have the mutation.
--When do you edit a gene?
An adult human body has billions of cells
in it, so correcting a gene defect in adults
is not an option. An ideal patient for gene
editing would have just one cell so that,
if the mutation in that single cell is corrected
the newly healthy cell can divide to more
healthy cells and eventually develop into
a healthy individual. The single cell from
which the ball of development starts rolling
is called a zygote.
It is formed from the fusion of the egg and
the sperm cells. It then multiplies to form
an embryo and, over the next six weeks, a
developing foetus.
--How did Mitalipov do it?
The most risky aspect of gene editing is accidentally
editing the wrong gene, causing problems that
can be passed down generations. This forces
us to confront many ethical issues (see below),
and this is also why gene editing studies
on human embryos is either banned or tightly
regulated around the world.
So first, Mitalipov had to receive the adequate
permissions and scientific and ethical reviews
in the US before his team was allowed to work
with human embryos. The scientists used sperm
samples from an HCM patient.
Among the two copies of the gene this individual’s
cells possessed, the MYBPC3 gene was mutated
in one while the other was healthy. The eggs
were obtained from a healthy female donor
(both copies of whose gene were healthy),
and they were fertilised with the sperm cells
in the lab.
A child born from such a union would have
a 50% chance of inheriting the HCM mutation
from the father. At this juncture, the scientists
used a five-year-old gene-editing technology
called CRISPR/Cas9.
CRISPR/Cas9 works like a customised pair of
scissors: they programmed it such that it
cut the gene at the start of the mutated part
(in this case a tiny missing section in the
MYBPC3 gene).
The cell notices this cut and proceeds to
repair it using the other copy of the gene
as a template. And since the other copy doesn’t
have the mutation, the cell repairs the cut
into a fully healthy one. Thus, the process
began with the presence of a mutation and
ended without it.
Previous experiments with CRISPR-Cas9 in human
zygotes have not been very successful. Sometimes
the embryos of edited zygotes were found to
consist of a mosaic of cells, some with the
mutation and some without.
To avoid this, Mitalipov started one step
earlier. He injected CRISPR/Cas9 into the
egg along with the sperm itself, rather than
after fertilisation. In this way, he was able
to produce embryos whose every cell was edited.
Ergo, no mosaicism.
Ever since its discovery in 2012 by Jennifer
Doudna, of the University of California, Berkeley,
and Emmanuelle Charpentier, from the Helmholtz
Centre for Infection Research, Germany
this technique has captured the imaginations
of people around the world because of the
ease, precision and efficiency with which
it allows scientists to edit genes. It was
even a favourite to win the 2015 Chemistry
Nobel Prize, though it finally didn’t.
links
https://www.cellecta.com
https://www.twistbioscience.com
https://www.paragongenomics.com/
