Scientific Cut-and-Paste: How CRISPR Gene Editing Is Impacting Our World
By Dawn Mangine
When KJ Muldoon was born, his parents and doctors quickly realized he was struggling to survive, but they weren’t sure why. Tests finally revealed a genetic disease was contributing to his failure to thrive, and without medical intervention, he was not going to live long. Fortunately for KJ, doctors were able to develop a treatment using CRISPR gene therapy, and 300 days after he was born, KJ was able to leave the hospital to live at home with his family.
What Is CRISPR?
Every living organism contains DNA, a chemical structure of bases, phosphates, and sugars. It’s like a long, spiral ladder, known as a double helix, with the bases as the rungs and the phosphates and sugars as the sides. DNA determines how a living thing looks and functions, with sections of DNA called genes carrying the relevant information about, for example, how tall a person is or whether their hair is curly or straight.
CRISPR stands for “clustered regularly interspaced short palindromic repeats,” which are short sequences of DNA strands. CRISPR allows scientists to alter DNA to remove mutations that are causing disease or dysfunction. While it sounds like something straight out of science fiction, it’s a natural process used by bacteria to protect itself against invading viruses.
In bacteria, CRISPR works by using CRISPR-associated protein-9 nuclease (Cas9) to snip part of an invading virus DNA and insert it into the bacteria's DNA, where it works like a "wanted poster," so the bacterium knows what the virus looks like. Then, those viral codes are copied onto RNA, which is a single strand of base code that carries genetic traits (similar to DNA). RNA is paired with Cas9 to target and destroy any recurring virus.
How to Edit Genes
In 2012, scientists figured out a way to use this system to target any DNA, not just viral DNA, in any organism. When they want to edit a gene, they design RNA to match the gene they want to edit and attach it to Cas9. The RNA acts like a guide, and directs Cas9 to the target gene. Cas9 then snips through the DNA.
Now the cell will try to repair itself, but it’s not always successful, and the gene can be turned off. In some cases, turning off the gene may solve the mutation, and nothing more needs to be done. However, scientists can take CRISPR one step further by adding template DNA, which acts like a blueprint to guide the repair process. This repairs a defective gene or inserts a new one, providing the gene with the desired trait.
Think of a tailor cutting a shirt and then sewing in fabric that has a different pattern, or construction workers rebuilding a damaged bridge. That is basically how gene editing works on a molecular basis.
Back to Baby KJ
KJ was born last year with a rare genetic disorder called carbamoyl phosphate synthetase I (CPSI) deficiency, meaning he lacked an enzyme that breaks down ammonia, a by-product of protein digestion. One way to treat CPSI is by getting a liver transplant, but that can take a long time and carries risks. With CRISPR, doctors were able to alter KJ’s DNA so his liver would produce the enzyme his body needed. Although he is not cured—he will need to undergo additional treatments and be monitored as he grows for other health conditions related to CPSI—he will be able to enjoy a normal life.
The Possibilities of CRISPR
CPSI isn’t the only genetic disorder that has been addressed using CRISPR. In 2023, the Federal Drug Administration (FDA) approved Casgevy, a cell-based gene therapy using CRISPR/Cas9, to treat sickle-cell disease (SCD), a very painful inherited blood disorder that can lead to disability and early death. For treatment, patients’ blood stem cells are modified to increase the production of fetal hemoglobin, a blood product that helps cells deliver oxygen. This provides patients relief from pain and organ damage—which is common with SCD—and helps them lead healthier, longer lives.
CRISPR can be used in any living organism to produce desirable genetic traits. Other ways scientists may use this method is to create drought-resistant crops, fruits and vegetables that stay fresh longer, and mosquitoes that can’t transmit diseases such as malaria. It also enables scientists to more closely study genes to see how they act and how turning them on or off affects an organism. CRISPR opens up a world of possibility for scientists.