The Fickle Reprive of the Sickle Cell Disease

The most common inherited blood disorder in the United States, and the condition that affects over 300,000 Africans every year, Sickle Cell Disease (SCD) is a dangerous, lifelong condition.

SCD is a genetic disorder caused by a mutation in both copies of a person's HBB gene. This gene encodes a component of hemoglobin, the oxygen-carrying protein in red blood cells. People with SCD have abnormal hemoglobin molecules - hemoglobin S - that stick to one another and form long, rod-like structures, causing sickle-shaped red blood cells. These cells often accumulate and cause clots or blockages, thus damaging vital organs and tissue.

For an individual to inherit SCD, both parents must have a faulty copy of the HBB gene (the gene that encodes a component of hemoglobin). However, if only one parent has the genetic defect, there is a 50% chance that the child will carry the sickle cell trait, but will not be affected by the disease.

A faulty copy of the HBB gene is required for a patient to be diagnosed with SCD. For a gene to be rendered faulty, instead of having an Adenine (A) nucleotide base pair in a key location in the DNA sequence, a Thymine (T) nucleotide will be present in its place.

While there are multiple SCD treatments currently in use, the main method involves replacing the patient’s bone marrow with that of a healthy, compatible donor to produce normal functioning hemoglobin - a risky process.

However, a team of researchers from the Broad Institute and St. Jude Children’s Hospital has been experimenting with a gene therapy method called base editing. Instead of transplanting bone marrow, this molecular technique recognises the mutated part of the gene that causes SCD, and changes a single letter of the genome.

While the effects of SCD cannot be completely reversed, the new base editing model developed allows scientists to change the Thymine (T) base pair to a Cytosine (C) base, thus producing a non-pathogenic variant of hemoglobin called Hb-Makassar.

Through bioengineering, the team of researchers created mice with the same defective hemoglobin causing the sickle shaped cells and genetically corrected the errors in the gene code. This resulted in a drastic reduction of sickled cells, leaving scientists hopeful for its effect on humans.

Works Cited

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Doctrow, Brian. “Fixing the Sickle Cell Disease Gene.” National Institutes of Health (NIH), 14 June 2021, www.nih.gov/news-events/nih-research-matters/fixing-sickle-cell-disease-gene#:~:text=Sickle%20cell%20disease%20(SCD)%20is.

Grossi, Giuliana. “New Estimate for the Risk of Child Mortality due to Sickle Cell Anemia in Africa.” HCPLive, 7 Mar. 2022, www.hcplive.com/view/new-estimate-risk-child-mortality-sickle-cell-anemia-in-africa.

John Hopkins Medicine. “Sickle Cell Disease.” Johns Hopkins Medicine Health Library, 2023, www.hopkinsmedicine.org/health/conditions-and-diseases/sickle-cell-disease.

National Heart, Lung, and Blood Institute. “Sickle Cell Disease - Treatment | NHLBI, NIH.” National Heart, Lung, and Blood Institute, 15 July 2022, www.nhlbi.nih.gov/health/sickle-cell-disease/treatment.

National Human Genome Research Institute. “About Sickle Cell Disease.” Genome.gov, 26 May 2020, www.genome.gov/Genetic-Disorders/Sickle-Cell-Disease#:~:text=Sickle%20cell%20disease%20is%20caused.