blood – BioQuakes

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.

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.

With over 150,000 diagnoses per year, cancer is the leading cause of illness and death in Australia. Cancers in organs such as the liver and kidneys often require surgery for a diagnosis, however, researchers have recently created a device to diagnose cancer that does not require invasive biopsy surgeries.

A biopsy can take many different forms. Some examples include a needle biopsy, the most general type, which is when a small needle is inserted into the skin to collect cells or fluid. An image-guided biopsy can include an x-ray, MRI, or ultrasound. A surgical biopsy is a surgery that includes making an incision in the skin in order to remove suspicious tissue. The complexity of the surgery varies depending on the the part of the body. Biopsies can be difficult for many reasons such as the price, the amount of risk, its consuming of time, and the possibility of bad side effects; however before this new method was finalized, they were necessary for a definite diagnosis and effective treatment.

Scientists have created a device called the Static Droplet Microfluidic device, which identifies the metabolic signature of cancer cells to identify ones that have broken away from a tumor and entered the bloodstream. Professor Warkiani states that the device has 38,400 chambers, which are capable of classifying the tumor cells, making it easier to distinguish a single cancer cell among billions of normal blood cells. This device is also crucial in discovering metastasis, which is when cancer cells travel through the blood and grow in different parts of the body. Metastasis leads to 90% of cancer-related deaths.

By <a href=”//commons.wikimedia.org/wiki/User:Cancer_Research_UK_uploader” title=”User:Cancer Research UK uploader”>Cancer Research UK uploader</a> – <span class=”int-own-work” lang=”en”>Own work</span>, CC BY-SA 4.0, Link

As learned in AP Biology, cancer cells are created when a cell loses its ability to regulate cell division. This inability could be caused by mutations that affect the activity of the cell cycle regulators. For example, a mutation could cause a lack of activity of cell cycle inhibitors, which allows the cell to continue to divide without limits. There could also be too much activity of positive cell cycle regulators, which can lead to cancer because it causes the cell to divide too much.

Differently from normal cells, cancer cells can continue to divide whether they have growth factors or not. Some have growth factors that are always “on,” some have the ability to make their own growth factors, and some can use neighboring cells to make growth factors for them. They also have “replicative immortality,” which is their ability to replicate many more times than the average cell. The enzyme telomerase is created, which reverses the shortening of chromosomes that normal cells experience during cell division. This characteristic is why cells have a limited life span. Cancer cells are difficult to stop because they do not undergo apoptosis (programmed cell death) like normal cells.

The Static Droplet Microfluidic Device will allow doctors to diagnose and treat cancers in a safe and cost-effective way. I have family members who have undergone painful surgeries in order to officially diagnose cancer, and technology using blood would have greatly improved their process of diagnosis. I invite any and all comments to share experiences or other information!

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: blood

Gene Editing Could Cure Sickle Cell Disease

New Technology Can Detect Cancer Using Blood Samples

By <a href=”//commons.wikimedia.org/wiki/User:Cancer_Research_UK_uploader” title=”User:Cancer Research UK uploader”>Cancer Research UK uploader</a> – <span class=”int-own-work” lang=”en”>Own work</span>, CC BY-SA 4.0, Link

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