As the lines between science fiction and reality continue to blur, one revolutionary development is blazing the way: CRISPR.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It was originally discovered as a defensive mechanism in bacteria. When bacteria become infected by viruses, a small piece of the viral DNA is inserted into the CRISPR region of the bacterium’s genome. When the same virus infects the bacterium again, the CRISPR DNA is transcribed to RNA, which serves as a guide to direct a Cas9 protein to a specific region of the viral DNA. The Cas9 protein then acts like scissors and cuts the viral DNA, thus riding off this infection. American scientist Jennifer Doudna and French scientist Emmanuelle Charpentier, the 2020 Nobel Prize laureates for chemistry, discovered how CRISPR works and showed that Cas9 protein and a guide RNA (gRNA) can be programmed to cut DNA in eukaryotic cells. This work set the stage for CRISPR-based gene editing technology.
CRISPR can be used for two main types of gene editing: gene disruption and gene replacement. These functions of CRISPR have many different applications, ranging from curing diseases to combating food insecurity. In the medical industry, the CRISPR gene editing technology is used to treat sickle cell anemia, restore vision, and boost cancer immunotherapy.
One notable example of CRISPR’s applications is its ability to treat sickle cell anemia (SCA). SCA is an inherited disease where patients have a mutation in a gene that encodes hemoglobin, which is a protein in red blood cells that helps oxygen move throughout the body. The defective hemoglobin in SCA patients causes red blood cells to curve in a “sickle” shape. This affects the red blood cells’ ability to bend and move, which can block blood
flow around the body. Blocked blood flow can lead to serious issues such as stroke, eye problems, infection, organ damage, and episodes of pain. There are no long term cures to SCA, so scientists turned to CRISPR. Scientists can remove cells from the bone marrow of the patient and use CRISPR to edit a defective gene, now allowing the red blood cells to produce normal hemoglobin. Victoria Gray, a thirty-nine-year-old Missouri resident, received this treatment and is the first person to be cured from sickle cell anemia. Since receiving this treatment, Gray says her quality of life and energy levels have increased. Gray has not needed any blood transfusions or other treatment since the procedure was first completed in June of 2019. CRISPR has opened the path in treating blood disorders, and this experimental treatment has now been used to treat multiple other patients with blood disorders like beta thalassemia.
CRISPR is also being used to restore vision to those with genetic disorders that cause deterioration of eyesight. To treat cancer, scientists and doctors take cells out of the patient, genetically edit them, and then place them back into the patient’s body. However, this is not possible with retinal cells, which are too fragile to be removed from the body. Scientists must turn to a different approach: using CRISPR to edit cells while the cells are still in the body. This is done by cutting small incisions in the retina and then injecting billions of copies of a harmless virus into the eye. Once in the eye, each of these viruses will be able to manufacture CRISPR to replace a defective gene in the genome with a normal gene. This will allow the production of normal proteins that can restore the function of cells in the retina. This approach is drastically improving vision for patients with Leber Congenital Amaurosis (LCA), a rare genetic disorder that causes the deterioration of vision starting at birth, eventually leading to total blindness. Michael Kalberer, a social worker from Long Island, has LCA and volunteered to have this CRISPR procedure done in the fall of 2021. He is now able to see color again after years of not being able to. In an interview with NPR, he described his experiences at his cousin’s wedding, saying happily, “I could see the DJ’s strobe lights change color and identify them to my cousins who were dancing with me!”
In the past few years, doctors have also been trying to use CRISPR to modify immune cells to treat recurring cancers with the goal of making patients’ immune cells to recognize and attack cancerous cells in their own body. Scientists take T-cells, cells of the immune system that fight infection and cancer, from the patient’s immune system and use CRISPR to edit them so that the immune cells can attack tumors while avoiding the healthy cells. The modified cells are then reinfused back into the patient. Former NBA player Victor Bartolome suffered from blood cancer and went through multiple treatments, including chemotherapy and stem cell transplant, and finally this CRISPR-based treatment method. Over a year later, he is still in remission. In principle, this experimental approach can be applied to many different types of cancer. These treatments are dubbed “living drugs” because living cells from the patient’s own immune system are engineered and reinfused back to the patient. Treating cancer with this method will continue to get more efficient in the next few years.
CRISPR has also been used to tackle food insecurity. At Washington State University, scientists are working to use CRISPR to replace selective breeding in livestock. For centuries, humans have tried to selectively breed livestock for those that produce more meat or have less disease. However, this process is slow and can cause many new problems while obtaining the desired trait.
Additionally, each time, only one male with the desired traits is available for breeding. Recently, scientists are trying to use CRISPR to directly edit animals’ genomes to make selective breeding more efficient. They have used CRISPR to sterilize male pigs and then implanted them with stem cells from a pig with the desired traits. The once sterile pigs will then produce offspring, all with the DNA from the desired pig. This process would allow farmers to have more breeding males and get more offspring from a desired pig, improving the efficiency of selective breeding. The goal of this treatment is to “increase the efficiency of food production,” according to lead researcher on this project, Jon Oatley. Oatley argues that by gene-editing livestock, we can strengthen the food supply and make sure that everyone has enough to eat.
CRISPR has transformed genetic engineering and its applications. Everything from food production to curing genetic disorders to saving lives from cancer has been accomplished with the help of CRISPR. It holds promise for advancing our knowledge and improving many aspects of lives.