AP Biology class blog for discussing current research in Biology

Tag: #SickleCellDisease

Gene Editing Could Cure Sickle Cell Disease

Do you know anybody with sickle cell disease? Sickle cell disease is the most common genetic blood disorder in the world. 70,000 to 100,000 Americans have it. It’s very likely that you know of someone who suffers from the disease or carries the gene.

Sickle cell anemia, a form of sickle cell disease, is caused by a gene mutation that changes the shape of the hemoglobin protein. The shape change causes blood cells which should be round, to be a sickle, curved shape. The deformed cells can clog blood vessels, causing severe pain and other dangerous symptoms. Another form of sickle cell disease is called beta-thalassemia which occurs when the body doesn’t produce enough hemoglobin and red blood cells, leading to low oxygen levels. As a result, children experience growth issues and fatigue.

Sickle Cell Anaemia red blood cells in blood vessels

CRISPR Therapeutics and Vertex have created a treatment called exa-cel, which uses gene editing to cure the disease for at least a year. In December of 2023, the FDA approved this treatment, making the U.S. the second country to approve a CRISPR therapy, following the U.K in November. A company called bluebird bio created another type of gene therapy called lovo-cel, which was approved by the FDA as well.

In exa-cel, the CRISPR system targets the genes that produce hemoglobin. Sickle celled anemia is caused by mutations in the gene HBB. The mutation distorts the structure of hemoglobin, which is what causes the blood cells to to have a curved shape instead of round. Exa-cel helps Cas9, an enzyme, target a gene called BCL11A. This gene stops the body from making a type of hemoglobin only found in fetuses. With Cas9, exa-cel cuts its DNA, which switches off BCL11A in bone marrow stem cells, where red blood cells are produced. As a result, the cells start making the fetal hemoglobin they were originally unable to produce, leading to the creation of healthy-shaped red blood cells. In this new treatment, doctors take out a person’s bone marrow stem cells, edit them with exa-cel, dispose of the rest of their untreated bone marrow, and then put the edited cells back in.

As learned in AP Biology, deletions in DNA can change the process of gene expression. The first part of gene expression is transcription, which happens in three steps: initiation, elongation, and termination. In initiation, the enzyme RNA polymerase binds to a region on a gene called the promoter. This then signals the DNA strand to unwind which allows the RNA polymerase to read the bases. Then in elongation, the RNA polymerase reads the DNA and makes an mRNA strand with complimentary base pairs. During termination, the RNA polymerase crosses a stop sequence, the mRNA strand is complete, and it detaches from the DNA strand. The mRNA then goes on to translation, which is when it is read to make proteins. When exa-cel deletes the DNA that codes for the BCL11A gene, it is never transcribed or translated, it is never expressed, and therefore the body can produce hemoglobin.

Since these modified cells replenish the body over time, exa-cel is seen as a “curative” treatment that is expected to last for the recipient’s lifetime. However, Vertex and CRISPR Therapeutics have only monitored most of their trial participants for less than two years. While nobody is certain that the treatment is permanent and without side effects, this type of gene editing is very significant to the scientific world, and could help thousands of people!

Exa-cel has be tested in about 100 individuals diagnosed with either sickle cell anemia or beta-thalassemia. However, in 2019, the FDA granted the companies a “fast-track” approval, enabling them to test the therapy in smaller groups than what is typically required.

In these ongoing trials, 29 of the 30 participants with sickle cell anemia didn’t experience any pain for one year following their exa-cel transfusions out of the 18 months under observation. Additionally, after receiving exa-cel, 39 out of 42 patients with beta-thalassemia didn’t require blood or bone marrow transplants (standard treatments for the disease) for one year. Vertex and CRISPR Therapeutics plan to track all participants for up to 15 years.

While some could arise earlier, so far the only negative side effects of the treatment are fever and nausea. Additionally, the FDA is worried that the Cas9 enzyme might stay active and cut the genome in places other than BCL11A, leading to what’s called off-target mutations. However, the companies looked into the places where the enzyme would most likely cut in the genome and luckily didn’t find any signs of this happening in the trial participants.
Similar to many gene editing treatments, exa-cel and lovo-cell are estimated to be very expensive. Vertex, CRISPR Therapeutics, and Bluebird Bio have not disclosed the price, but projections indicate they could reach up to $2 million per patient. It is also unclear whether or not the treatment would be covered by insurance, specifically government programs like Medicaid. This is of particular concern given that sickle cell disease predominantly affects people of African descent. African Americans are more reliant on public insurance like Medicaid compared to other groups in the United States.
These treatments are a huge breakthrough in science and could help thousands of people. Unfortunately, they are inaccessible to most people. What do you think these companies can do to make them more accessible? I invite any and all comments to share!

A New Cure: CRISPR Technology’s Role in Curing Sickle Cell Disease

Affecting more than 100,000 people in the US, SCD, or sickle cell disease, is an inherited condition that causes a person’s blood cells to block blood flow to the rest of the body. In extreme cases, this disease can cause strokes, eye problems, and many other severe adverse effects in somebody with the illness. As of now, the leading treatment is medication; however, this medication can come with side effects such as lower white blood cell levels and platelet count. Recently, though, a ScienceNews article highlighted a new cure for Sickle Cell Disease that was approved by the Food and Drug Administration.

Sickle Cell Anemia

In the article, a CRISPR gene-editing technique is used to cure the disease. The treatment alters the gentic blueprint of the bone marrow that makes blood cells in a patients body. This process uses a patients own cells to defeat Sickle Cell disease by having edited cells make fetal hemoglobin. Fetal hemoglobin, unlike normal hemoglobin, cant be turned sickle and therfore wont clog up blood streams. In a study following people who received this treatment, 29 out of 30 didnt report any pain crises for a year. There are still side effects of this treatment such as increased exposure to cancer due to chemotherapy needed in the bone marrow altering and potentially other undiscovered sideffects. However, the treatment is still relatively new and it is yet to be seen if it can be improved on and it also still may be a better alternative than the current treatments of Sickle cell disease.

Being a carrier for the sickle cell gene myself, I find this research very interesting. Sickle Cell disease has an autosomal recessive pattern which means that the way to express Sickle Cell disease is through getting two of the recessive genes from both of your parents. Therfore somebody who is heterozygous for sickle cell has a higher chance of having a child with sickle cell disease if there partner is either a carrier or has sickle cell disease than somebody who homozygous dominant for not having sickle cell disease. With this topic being so closely related to me it is important that scientists continue to discover and improve on their ways of curing sickle cell disease in the upcoming generations. If you know any information about any other emerging cures for sickle cell disease share them in the comments below!


New Advancements in Curing Sickle Cell!

Do you know someone who has sickle cell or has passed away at the hands on sickle cell? Well, new treatments using CRISPR technology are under way. This revolutionary treatment is made to last much longer than previous gene editing treatment, which lasted for up to a year. This treatment is called exa-gel made by Vertex and CRISPR. 


How Does It Work?

In sickle cell anemia, mutations in a gene HBB causes a change in the hemoglobin’s structure, causing circular red blood cells to twist into a sickled shape. The sickled red blood cells cause extreme pain and fatigue. In severe cases, beta-thalassemia can occur. Beta-thalassemia causes not enough hemoglobin or red blood cells to be produced, leading to low oxygen levels.  The exa-gel technology targets the hemoglobin protein. It directs the Cas9 enzyme to the BCL11A gene and cuts its DNA off, turning it off. It is then able to produce fetal hemoglobin with normal shape. For this to be done, physicians must remove the bone marrow stem cells, edit them with the exa-cel, destroy the untreated bone marrow, and reinfuse treated cells. In AP Biology, we learned how the regulation of gene expression works. A gene that is usually on but can be turned off is a repressible operon. The operon regulates genes with the help of enzymes. The operator site is where repressor proteins can bind to turn off production. It is in between the promoter and structural genes. Usually, RNA polymerase binds to the promoter to begin production. Once that occurs, mRNA is transcribed. Then, tRNA picks up amino acids and the anticodons bind to the codons for the polypeptide chain to form. Finally, proteins will be produced to allow for the desired outcome to occur. However, Cas9 inhibits this process so that these sick blood cells will not be produced and healthy fetal ones will begin production. 



The Future

While this new technology seems exciting, there are a lot of uncertainties about it. First of all,  “the participants have only been tracked for a short time and that problems could arise later.” Although we do not know much about the long term effects of the treatment, we do see promising results. 29/30 of participants with sickle cell anemia reported no pain for a year after the treatment. 39/42 of beta-thalassemia no longer needed blood or bone marrow transfusions for a year after it. Sadly, it is expected for the treatment to cost about $2 million per patient. Due to this absurdly high cost, scientists are looking into a technique called haploidentical transplant to treat sickle cell anemia. This technique, which is also used for cancer, involves replacing a patient’s bone marrow with a parent or sibling who shares 50% of their DNA. 88% of patients with this procedure made normal red blood cells 2 years after it. This procedure is promising and much more cost effective; it could be popular in low income countries. Nevertheless, this new technology is extremely exciting and potentially world altering.

Breaking the Chains of Sickle Cell: A New Dawn with Gene Therapy

The U.S. Food and Drug Administration has made a significant advancement in the treatment of sickle cell disease (SCD) by approving two new cell-based gene therapies, Casgevy and Lyfgenia, for patients aged 12 and older. Sickle cell disease is a genetic blood disorder that affects about 100,000 people in the U.S., predominantly African Americans, and is characterized by a mutation in the hemoglobin protein. This mutation leads to red blood cells adopting a crescent shape, which can obstruct blood flow and oxygen delivery, causing severe pain, organ damage, and potentially life-threatening complications.

The mutation in the hemoglobin protein that characterizes sickle cell disease (SCD) alters the structure and function of hemoglobin, which is crucial for transporting oxygen in the blood.  Hemoglobin is made up of four protein subunits, and in SCD, a mutation occurs in the gene that codes for the beta-globin subunit. This mutation leads to the production of an abnormal form of beta-globin known as hemoglobin S (HbS). In normal RBC (red blood cells), hemoglobin (a protein) has a particular shape. We learned in AP biology that proteins need a specific shape to carry out their function. In people with sickle cell anemia, that protein is mutated doesn’t have the correct shape, and cannot carry out its function.  The reason it doesn’t have the right shape is that the mutated hemoglobin sequence is modified at a single amino acid.

Under certain conditions, such as low oxygen levels, dehydration, or acidosis, HbS molecules tend to stick together, forming long, rigid chains within the red blood cells. These chains distort the shape of the red blood cells from their normal, flexible disc shape to a rigid, crescent or “sickle” shape. Unlike normal red blood cells that can easily move through the bloodstream, these sickled cells are stiff and sticky. Its interesting how such a small change can have such a significant effect in our body!

The crescent-shaped cells can get trapped in small blood vessels, blocking the flow of blood. This blockage prevents the delivery of oxygen to nearby tissues, which can cause pain and damage to tissues and organs. Furthermore, the sickled cells are more prone to breaking apart, leading to hemolysis (the destruction of red blood cells), which can cause anemia (a shortage of red blood cells) and other complications. The recurring blockage of blood vessels and the chronic shortage of red blood cells and oxygen supply lead to the severe symptoms and complications associated with sickle cell disease, including acute pain crises, increased risk of infections, and organ damage.

Casgevy stands out as the first therapy of its kind to employ CRISPR/Cas9, a groundbreaking genome editing technology, to modify patients’ hematopoietic stem cells. This process aims to increase the production of fetal hemoglobin in patients, which helps prevent the sickling of red blood cells. On the other hand, Lyfgenia uses a lentiviral vector to genetically modify blood stem cells to produce a variant of hemoglobin that reduces the risk of cells sickling. Both therapies involve modifying the patient’s own blood stem cells and reintroducing them through a one-time infusion, following a high-dose chemotherapy process to prepare the bone marrow for the new cells.


These therapies represent a major leap forward in treating sickle cell disease, addressing a significant unmet medical need for more effective and targeted treatments. The FDA’s approval of Casgevy and Lyfgenia is based on the promising results of clinical trials, which demonstrated a substantial reduction in the occurrence of vaso-occlusive crises, a common and painful complication of SCD, among treated patients.

The approval of these therapies also underscores the potential of gene therapy to transform the treatment landscape for rare and severe diseases. By directly addressing the genetic underpinnings of diseases like SCD, gene therapies offer a more precise and potentially long-lasting treatment option compared to conventional approaches. The FDA’s support for such innovative treatments reflects its commitment to advancing the public health by facilitating the development of new and effective therapies.

However, it’s important to note that these therapies come with risks and side effects, such as low blood cell counts, mouth sores, and the potential for hematologic malignancies, particularly with Lyfgenia, which carries a black box warning for this risk. Patients receiving these treatments will be monitored in long-term studies to assess their safety and effectiveness further. Despite these challenges, the approval of Casgevy and Lyfgenia marks a hopeful milestone for individuals with sickle cell disease, offering new avenues for treatment and the promise of improved quality of life. If you were diagnosed with Sickle cell disease, would you try this no-treatment when available? Do the positives outweigh the negatives? Let us know!

Powered by WordPress & Theme by Anders Norén

Skip to toolbar