I’m sure you have heard of CRISPR. You know, gene editing, modifying DNA… that sort of stuff. But you probably didn’t know that CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Fancy name, right? The wonders of gene therapy are something that has always intrigued me because of its potential to help so many people.
CRISPR was first discovered in microbes like bacteria and archaea all the way back in 1987. Through decades of research, scientists were able to better grasp the functions and capabilities of CRISPR. A simple way to understand it is to imagine an immune system. Bacteria and archaea use CRISPR to protect themselves from viruses by detecting and eliminating the viruses invading them. In humans, we develop antibodies to defend ourselves, and CRISPR does the same, except in a “genetic” sense. When a virus injects its DNA into the bacterial cell, a part of the virus’s DNA is inserted into the bacteria’s genome. This creates a genetic record of past infections, which are then copied into RNA sequences that are split into individual units. A Cas9 protein is formed which serves to recognize the virus DNA through sequence complementarity, bind to it, and destroy it (Qi, 2024).
So, how do we utilize CRISPR in our medical treatments? Gene therapy can do a few things: cut, delete, and insert. It can replace a gene with a different one, deactivate a non-functioning gene, or introduce a new and modified gene. Ultimately, it’s able to fix mutated genes and manage the expression of genes in protein products. Because CRISPR uses these “guide RNAs,” it is able to target specific sequences and cut more precisely. That’s one of the major advantages of this technology: its accuracy and simplicity, which in turn leads to reduced costs and risks involved (Qi, 2024).
When it comes to the actual application of gene editing, there are two fields that you should consider. The first is the treatment of genetic diseases through targeting the specific genes that cause the disease. An example of this is sickle cell anemia, a rare disease solely contracted through genetic inheritance and deals with a mutation in the hemoglobin (protein) of the red blood cells. More specifically, sickle cell anemia is when your regular red blood cells become rigid, C-shaped cells that make it difficult to flow through blood vessels and are unable to carry as much oxygen, which leads to several other health complications. In 2023, the FDA approved the first-ever CRISPR/Cas-9 gene therapies that can treat sickle cell disease patients. The first gene therapy is called Casgevy. Casgevy works by taking the patient’s hematopoietic stem cells, modifying the DNA, and inserting it back into the patient’s bone marrow where it multiplies and increases the production of fetal hemoglobin (which reduces the sickling of cells). Lyfgenia, the second approved cell-based therapy, operates in a similar way, except the blood stem cells are modified to produce HbAT87Q, allowing it to function more like the normal hemoglobin A (“FDA Approves First,” 2023).
Gene editing can also be used to treat diseases through cell therapies. Cell therapies, although similar to the processes I described earlier, differ as they more so pertain to cancer diseases. For example, when treating leukemia, chemotherapy is typically used to eliminate the tumor cells. However, CRISPR offers an opportunity to more effectively get rid of these tumors. CRISPR can be used to modify the T cells – white blood cells that fight infections – so that when they are injected back into the patient, they can more precisely attack tumors. Although, the side effects and success rate of this type of treatment have not been determined yet (Qi, 2024).
Those two instances illustrated mainly have to do with ex vivo strategies, where cells are taken out and then put back in. But there are also in vivo ways of editing cells where the CRISPR is packaged in a transport vehicle, such as lipid nanoparticles, and inserted into specific areas of the body (“Gene Editing,” n.d.).
Of course, all medical advancements come with limitations. There is still so much research to be done on CRISPR, and these limitations should be seen as opportunities to overcome such obstacles. One setback is how CRISPR is not able to efficiently deliver to mature cells at a large scale. It is also not 100% accurate, meaning it cannot be utilized and applied to the vast variety of patients dealing with unique genetic mutations and diseases yet (“What is CRISPR,” n.d.).
Lastly, I think it’s important to briefly touch upon the ethical issues that come with something as big as gene editing. One major ethical debate that arises from CRISPR is the improper use of this technology to edit genomes in the gametes to create more desirable traits in the offspring. The idea of enhancements on appearance and intelligence to create this “designer baby” is seriously unethical because it further deepens socioeconomic inequalities as the rich get the upper hand when accessing this technology. It’s crucial that guidelines and restrictions are in place so that CRISPR is used responsibly for medical treatments and cures only (Qi, 2024).
Overall, I’m super excited to see what CRISPR has yet to offer and what scientists discover in the future!
Works Cited
FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. U.S. Food and Drug Administration. (2023, December 8). https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
Gene editing. CRISPR Therapeutics. (n.d.). https://crisprtx.com/gene-editing
Qi, S. (2024, June 10). Stanford explainer: CRISPR, gene editing, and beyond. Stanford Report. https://news.stanford.edu/stories/2024/06/stanford-explainer-crispr-gene-editing-and-beyond#what-CRISPR What is CRISPR?. The Jackson Laboratory. (n.d.). https://www.jax.org/personalized-medicine/precision-medicine-and-you/what-is-crispr