Sickle cell anemia
- CRISPR gene editing tool is used as a gene therapy for
sickle cell anemia patients.
- The mutated gene was 'corrected' in the hematopoietic
stem cells using the CRISPR tool.
- The treated cells were found to thrive after 16 days,
paving the way for better treatment modalities for sickle cell anemia.
is a group of
inherited disorders that lead to a sickle shape of red blood cells which could
block blood vessels, preventing transport of oxygen. The blocked arteries can
lead to a painful situation called pain crisis and the damage to organs and
tissues, over time. There is no treatment for this condition, but a new study
by researchers from Stanford University has shown that the gene editing tool
CRISPR could be used to treat people with sickle cell
The gene editing tool
was used to successfully result in normal hematopoietic stem cells and this was
transplanted into mice. The team of researchers believe that this method could
be used to treat different blood borne genetic disorders like sickle cell
anemia and thalassemia.
‘CRISPR, the gene editing tool could aid in eliminating genetic disorders such as sickle cell anemia and thalassemia.’
Sickle Cell Anemia
This genetic condition
is caused by a single gene mutation that leads to faulty hemoglobin molecules
that are stiff and give the red blood cells a sickle shape. The red blood cells
are normally flexible and go through blood vessels with relative ease. However,
the stiff and faulty red blood cells in sickle cell patients could get lodged
in the blood vessels and cause pain, along with poor oxygen-related damage to
The disease was first
discovered in the tribals of The Nilgiris hills in Tamilnadu but a higher
prevalence has been identified in populations in Central India.
- 70,000 to 100,000 Americans are affected
- In Indian tribals, the incidence is between 1 to 40%
- In high-income countries, this condition is managed by
treating symptoms and through blood transfusions.
- In low-income countries, sickle cell anemia leads to death
before the age of 5 years.
women with sickle cell anemia are found to deliver low birth weight babies,
with a high risk of maternal mortality at birth.
Promise of Gene Therapy
Mathew Porteus, who is
the senior author of the study and an associate professor of Pediatrics, said
"What we've finally shown is that we can do it. It's not just on the
chalkboard. We can take stem cells from a patient and correct the mutation and
show that those stem cells turn into red blood cells that no longer make
Professor Porteus and
colleagues have been working on a gene therapy method of treatment for sickle
cell anemia for many years, but they have been using an older gene editing
tool. According to the professor, the older method took half a dozen years to
carry out the alteration in the gene while CRISPR took less than a week and it
worked much better than the earlier tool.
The CRISPR/Cas 9 system
is a mechanism that is resent in bacteria to help it to prevent the growth of
viruses. When the viral DNA enters the bacteria, the Cas 9 system is taken to
the sequence complementary to the CRISPR sequence in the genome of the virus,
cleaving the genome. The CRISPR sequence is generated from a previous exposure
to the viral DNA. This defense mechanism has been adopted as a tool by
scientists Jeniffer Doudna and colleagues to create a gene editing mechanism
that cleaves target DNA and alters it.
Correcting the Mutation
Porteus and colleagues
collected hematopoietic stem cells, cells that develop into blood cells, from
sickle cell anemia patients and corrected the mutations using CRISPR. They
concentrated these stem cells so that 90% of the cells were corrected to normal
hematopoietic stem cells.
hematopoietic cells were injected into mice. They colonized in the bone marrow
and started generating normal red blood cells. When the blood of the mice was
tested after a period of 16 weeks, the corrected red blood cells were found to
CRISPR/Cas 9 system
- A patient does not show any symptom if the percentage
of sickle cell red blood cells is below 30%.
- The life span of a sickle red blood cell is only 10
days while the life span of a normal red blood cell is 120 days.
- As the sickle cell red blood cells die soon and the
normal cells live longer, the normal cells soon become more in number,
with a reduction in the number of sickle cell red blood cells.
is a widely
used gene editing tool that has received popular support from many research
laboratories in the world. It was recently used in a human trial by Chinese
researchers on end-stage cancer patients. However, there is a certain caution
that is meant to be exerted while using this technology.
Some scientists believe
that there could be unprecedented immune response due to the use of this
technology or it could lead to unwanted mutations in regions of the genome,
where the sequence could be similar but not exact. However, latest studies have
shown that naturally occurring proteins could turn off CRISPR, allowing
mutations only in regions of the genes that are dictated. This will help in
regulating this gene editing tool and safeguard it from causing unnecessary
The current study by
Porteus and colleagues, if proven successful in a clinical trial, could improve
the quality of life of a patient with sickle cell anemia. The gene therapy,
made possible by CRISPR, could be the cure that would rid of symptoms
associated with sickle cell anemia.
- What Is Sickle Cell Disease? - (https://www.nhlbi.nih.gov/health/health-topics/topics/sca)
- Sickle cell disease in India: A perspective - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822363/)
- Sickle cell disease in tribal populations in India - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510747/)