including sickle cell anemia and thalassemia are caused due to genetic
mutations resulting in abnormal production of red blood cells.
- Increasing fetal
hemoglobin (HbF) levels is a possible cure to diseases like sickle cell
- Gene therapy was
used to introduce a naturally favorable mutation in blood forming tissue
that in turn increases HbF levels.
was used to turn on the fetal hemoglobin (HbF) gene in
HUDEP-2 cells (adult human red
blood cell precursor), which is a model of the cells that form red blood
cells in humans. HbF gene is usually turned off after birth resulting in low
fetal hemoglobin levels. However, some individuals have increased HbF levels
even in adulthood, a condition called Persistence
of Fetal Hemoglobin (HPFH). Further, increased HbF levels in individuals
suffering from genetic blood disorders result in milder symptoms. Introducing
the HPFH responsible mutation in sickle cell anemic and thalassemia patients
may ultimately lead to a cure for these hemoglobinopathies.
including sickle cell anemia (SCA) and thalassemia are diseases that have
damaged or abnormal hemoglobin production. Hemoglobin is the oxygen-carrying
molecule in blood cells that transport oxygen throughout the body. Thereby,
hemoglobinopathies are inherited blood disorders that result in abnormal or
quantitative or qualitative hemoglobin production.
is an inherited red blood cell disorder where the cells acquire a sickle shape
instead of the normal spherical shape. This is caused due to a single mutation
in the hemoglobin beta gene. The sickle cells have reduced oxygen carrying
capacity and get clogged in blood vessels leading to anemia and severe pain.
Since it is inherited in an autosomal recessive manner, a child may be affected
if both parents are affected or if both parents are
carriers for the mutation.
‘Addition of the naturally occurring beneficial British-198 mutation in patients with genetic blood disorders elevates their fetal hemoglobin level and thereby reduces symptoms.’
is also an inherited blood disorder
that affects the production of hemoglobin. In this disease the body is unable
to produce hemoglobin or is able to do so in an insufficient amount. Depending
on which gene is mutated thalassemia maybe alpha or beta thalassemia.
Thalassemia maybe caused due to various mutations in hemoglobin production
treatments for hemoglobinopathies
- Blood transfusion
- Bone marrow
However, all these have potential ill effects. While medications
have a wide range of side effects, blood transfusion has possibilities of
infection and rejection. Bone marrow transplants, on the other hand, have an
additional burden of finding a matching donor.
is a procedure that involves treating genetic diseases at the root cause, the
genes. It uses one of the following to do so:
a faulty disease causing gene with a healthy one
or knocking out a faulty gene
new genes to help fight disease.
In this study conducted at the University of
New South Wales, researchers introduced a mutation using CRISPR into model
human blood cells to increase fetal hemoglobin (HbF) levels. According to
previous studies, it was identified that some patients with blood disorders
carried an inborn natural mutation that resulted in 20% more HbF levels which
resulted in milder symptoms of the disease. This extra fetal hemoglobin has
strong affinity for oxygen and hence performs the function of the defective
adult hemoglobin. This factor was put into practice in this study published in
the journal Blood
Out of the many variants of the naturally
occurring mutation, British-198 was used for the study. It is called so because
it was first identified in a British family and the mutation occurs in the
198th nucleotide position of the gene. The British-198 was introduced into
HUDEP-2 cells. The cells that were edited showed substantially elevated levels
of HbF. This gene editing therapy maybe used as a therapy for blood disorders
if the British-198 mutation is introduced in the blood forming stem cells from
Concluding with the words of the senior author,
Professor Merlin Crossley, "Because this mutation already exists in nature and
is benign, this 'organic gene therapy' approach should be effective and safe to
use to treat, and possibly cure, serious blood disorders. However, more
research is still needed before it can be tested in people."
- Beeke Wienert, Gabriella E. Martyn, Ryo Kurita, Yukio Nakamura, Kate G.R. Quinlan, Merlin Crossley. KLF1 drives the expression of fetal hemoglobin in British HPFH. Blood, 2017; blood-2017-02-767400 DOI: 10.1182/blood-2017-02-767400
- What is gene therapy? - (https:ghr.nlm.nih.gov/primer/therapy/genetherapy)