Gene Editing Techniques on Track to Become Prioritized Treatments for Diseases, Cancers
Genetic engineering practices that have been approved or await approval from the FDA to treat patients with sickle cell anemia, beta thalassemia, leukemia and more.
Photo Source: The Scientist
Genetic engineering and CRISPR technology may still sound like a thing of dystopian or futuristic fiction to many, but since it arrived in the modern biology scene 10 years ago, it has undergone development that may point to it as a potential cure for the previously-believed incurable.
From blood disorders, to blood cancer, to blindness, researchers and medical professionals are looking at the advanced technology as possible best-in-line treatment for diseases and disorders that affect millions.
In this letter, we’ll look at a couple of diseases where gene editing has advanced and may be prioritized as treatment or approved as a cure in the next few years.
Sickle Cell Anemia and Beta Thalassemia
Sickle cell anemia and beta thalassemia are blood diseases caused by heritable, single-gene mutations.
For sickle cell anemia, there is a mutation in hemoglobin proteins, which causes them to become misshapen, or sickled, and break down, reducing their ability to carry oxygen throughout the body. The cells can clog blood vessels, causing severe pain and putting patients at risk of organ damage and strokes. Approximately 300,000 infants are born with the disease annually.
Beta thalassemia is a blood disorder where the body makes little or no functioning hemoglobin. About 60,000 infants are born with the disease annually.
Current treatment for the disorders include medications, blood transfusions and bone-marrow transplants, with the focus being on avoiding chronic pain, relieving symptoms and preventing complications.
Shifting away from just making patients feel more comfortable living with the disorders, researchers are using genetic engineering to race toward a cure.
Video Source: NHLBI
In 2020, researchers used CRISPR techniques to counter sickle cell anemia and beta-thalassemia, according to Science. The researchers removed patients’ blood stem cells from their bone marrow and activated the gene that produces usable hemoglobin. They administered chemotherapy to the patients to rid them of their diseased cells, then infused the altered stem cells.
The process allows a restoration of missing hemoglobin in beta thalassemia patients and replaces some of the flawed hemoglobin in sickle cell anemia patients. Patients who underwent the study were able to make sufficient levels of healthy hemoglobin and showcased no sickle cell crises or, barring the exception of one case, needed a blood transfusion.
CRISPR Therapeutics and Vertex Pharmaceuticals have partnered to develop this treatment, which they call exa-cel. It is currently being used in five clinical trials. In September 2022, the FDA granted exa-cel a rolling review as a potential one-time treatment for sickle cell anemia and transfusion-dependent beta-thalassemia. If approved, exa-cel will be the first CRISPR therapy to achieve regulatory approval for a genetic disease.
According to The Harvard Gazette, a team of Harvard and Broad Institute researchers used CRISPR-Cas9 technology in a 2021 study to successfully treat sickle cell disease in mice. The researchers changed a single letter of DNA in the mice’s red blood cells to correct the mutation in hemoglobin that causes the disorder. This technique uses a molecular tool that allows them to change the letters of gene pairs instead of making a double-stranded break in DNA.
“The base editing approach we published offers a unique combination of benefits where we are getting rid of the disease-causing mutation,” said David Liu, a researcher in the study, to The Harvard Gazette. “We’re not simply trying to compensate for it by adding more non-diseased hemoglobin. We’re actually getting rid of the disease, the hemoglobin that’s the root cause of the problem.”
Editas Medicine, Inc. is taking a slightly different approach — in vivo instead of ex vivo like the therapies aforementioned — with EDIT-301. This treatment edits the regions of two genes to reduce the misshaping of red blood cells. Although in its earlier stages compared to exa-cel, EDIT-301 shows promise, as one patient was successfully treated for sickle cell disease.
Cancer
Within the broad range of cancer — with treatability affected by the type and stage of the cancer — CAR T-cell therapies may present a miracle cure.
White blood cells, also known as T-cells, are the body’s first line of defense against pathogens. T-cell therapies program cancer patients' immune cells to recognize and target cancerous cells.
According to Scientific American, using this technology, which was first published in a 2010 study for the treatment of lymphoma by Steven Rosenberg, chief of surgery at the National Cancer Institute, a patient’s T-cells are removed and genetically altered to build cancer cell receptors. The cells, which can now detect and attack cancer cells, are infused into the body and reproduce to build up the body’s defense.
In 2016, researchers at the University of Pennsylvania used a CAR T-cell treatment called tisagenlecleucel for patients with acute lymphoblastic leukemia (ALL), a cancer where a DNA mutation of bone marrow cells causes the production of underdeveloped white blood cells. The remission rate of treated patients was about 85 percent. The FDA approved the therapy as a treatment for ALL.
Intellia Therapeutics has developed a CRISPR-powered T-cell therapy called NTLA-5001, which uses gene editing to reprogram patients’ immune cells ex vivo. It has been used on patients with acute myeloid leukemia (AML), a white blood cell cancer that affects blood and bone marrow. AML patients generally have a five-year survival rate with available treatments. Intellia dosed its first patient with the treatment in March 2022 and was granted orphan drug designation by the FDA for the treatment of AML a few days later.
The effectiveness of T-cell therapy is not exclusive to blood cancers — it presents a potential solution for other cancers, such as the pancreatic kind. A 71-year-old pancreatic cancer patient displayed regression of her tumor after being treated with T-cell therapy.
This technology can mean a new lease on life for those affected by incurable diseases. It can be the difference between buying patients comfort and time with fully restoring their health.
Best,
Christina for the Don’t Count Us Out Yet Team