Gene Therapy
Evolutionary Development
In the late 1960s, scientists
first demonstrated the
feasibility of incorporating
new genetic functions in
mammalian cells. They used
several methods, One
involved injecting genes with
a micropipette directly into a
living mammalian cell.
Another exposed cells to a
precipitate of DNA containing
the desired genes.
One of the first people to
report the direct
incorporation of functional
DNA into a mammalian cell
was Lorraine Kraus at the
University of Tennessee. she
managed to genetically alter
the haemoglobin of cells
from bone marrow taken
from a patient with sickle-cell
anaemia in 1961. Seven
years later, Theodore
Friedmann, Jay Seegmiller
and John Subak-Sharpe at
the National Institutes of
Health (NIH), Bethesda,
successfully corrected
genetic defects associated
with Lesch-Nyhan syndrome,
a debilitating neurological
disease. They did this by
adding foreign DNA to
cultured cells collected from
patients suffering from the
disease. The first humans to
receive gene therapy took
place in 1970. It was
administered to two very
young West German sisters
suffering from
hyperargininemia, an
extremely rare genetic
disorder that prevents the
production of arginase. But
Disappointingly none of the
sisters responded to the
treatment.
In the early 1970s, A new
pathway for gene therapy
opened up with the
development of genetic
engineering. The technique
provided two key tools.
Success stories Failures
One such success story One of the failures of the
stemmed from the gene therapy happened
Nationwide Children’s with the first humans to
Hospital, Ohio. In this receive gene therapy took
2017 study published by place in 1970. It was
the research team in New administered to two very
England Journal of young West German
Medicine, 15 patients with sisters suffering from
spinal muscular atrophy hyperargininemia, an
type 1 (SMA1) received a extremely rare genetic
single dose of gene disorder that prevents the
therapy with a goal of production of arginase.
functionally replacing the This is an enzyme that
mutated gene. Subjects helps prevent the build up
that underwent gene of arginine in bodily fluids.
therapy showed signs of Any accumulation can
motor improvement which cause brain damage,
are otherwise absent epilepsy and other
when untreated. A neurological and muscular
significant part of this gene
problems. Each sister
therapy success can be received an injection of a
attributed to an rabbit virus (Shope
unassuming, vital papilloma) known to induce
contributor – a delivery the production of arginase.
virus. The injection was given as
a last desperate measure
Year 2017, Sickle-cell to rescue the children. The
cure, in March, treatment was carried out
researchers announced by Stanfield Rogers, an
that a teenage boy in American physician,
France had been cured of together with H. G.
sickle-cell disease after Terheggen, a German
receiving an experimental paediatrician. They took the
gene therapy developed risk based on observations
by Bluebird Bio. Caused Rogers had previously
by a single genetic made with some laboratory
mutation, sickle-cell is an technicians at Oak Ridge
inherited blood disorder National Laboratory who
that affects 100,000 became infected with the
people in the U.S. and rabbit virus when working
millions around the world. with it. None of the
Scientists removed stem technicians experienced ill-
cells from the boy’s bone effects from the virus but
marrow and modified them had abnormally low levels
in the lab by introducing of arginine in their blood.
copies of a gene to This was apparent even in
prevent his red blood cells a technician whose last
from becoming “sickled.” exposure to the virus had
When the treated cells been 20 years before.
were infused back into his Rogers connected the
body, they began to make technicians’ abnormal
normal blood cells. More arginine levels with a gene
than two years after in the rabbit virus which
treatment, the patient has was known to encourage
enough normal red blood the production of arginase
cells to evade any side in rabbits. By giving the
effects of the disorder. rabbit virus to the girls,
Rogers hoped to transfer
Firstly, a means to clone
specific disease genes.
Secondly, an efficient
method for gene transfer. US
scientists Theodore
Friedmann and Richard
Roblin hightlighted the
potential of the technology
for gene therapy. The
technique was first tried out
in the case of beta-
thalassemia.
In the 1980s Gene therapy
entered a new era, the
discovery of retroviruses
which proved a much more
efficient tool for gene
transfer. The first suitable
retroviral vector for gene
therapy was developed by
Richard Mulligan, a chemotherapy, don’t work.
researcher at Massachusetts
Institute of Technology and
former doctoral student of
Paul Berg, a key pioneer in
genetic engineering at
Stanford University.
Despite the difficulties, gene
therapy began to turn a
corner the following decade,
aided by the arrival of safer
and more effective vectors.
Positive results began to be
reported for a number of
gene therapy trials. Most
were small-scale academic
studies. In 2007 Jean
Bennett, an ophthalmologist
at the University of
Pennsylvania, demonstrated
in a small trial that gene
therapy could provide a
promising treatment for
inherited retinal disease.
In 2015 Subsequent trials in
more patients carried out,
gene therapy was found to
help haemophilic patients, a
number of whom no longer
needed to take blood clotting
factor drugs. In 2016 Europe
licensed a second gene
therapy, developed by
GlaxoSmithKline for children
suffering from ADA-SCID. A
year later Novartis secured
approval for the first gene
therapy in the United States.
Cancer killers genetic instructions to their
This year the FDA cells to produce arginase.
approved two pioneering After the two sisters were
treatments, Kymriah and treated a third sister was
Yescarta, that use a born afflicted with
patient’s own immune hyperargininemia. She was
cells to fight rare types of also injected with the virus.
cancer. Called CAR-T Disappointingly none of the
therapies, these “living sisters responded to the
drugs” are made by treatment.
extracting T cells from
patients and genetically
engineering them to go
after and destroy cancer
cells. The cells are then
infused back into the body.
So far, these therapies are
being tested only in a
handful of lethal cancers
as a last resort when more
traditional treatments, like
Kymriah treats a bone
marrow cancer that affects
children and young adults,
and Yescarta treats a type
of lymphoma. Some
patients have had
remarkable recoveries and
remain in remission
months or years later.
Building new skin
When a bacterial infection
threatened his life, a boy
with a devastating
connective tissue disorder
called epidermolysis
bullosa got new skin
created with gene therapy.
To make it, scientists
extracted cells from a part
of the child’s body that
wasn’t blistered. They
isolated skin stem cells
and added copies of a
healthy version of the
gene. They let these cells
grow into small sheets
and, in a series of three
surgeries, transplanted
them onto the patient’s
body at a hospital in
Germany. Researchers
announced the
groundbreaking skin graft
in November.
All these scientist worked
hard to develop gene therapy
and through decades of
research and study, it was
successfully developed. In
the near future, as scientist
continue to widen their study
regarding with gene therapy,
we are all hoping for a
successful outcome that
would benefit us all.