The First CRISPR Baby

CRISPR is a new gene editing technique that fixes problematic DNA sequences called mutations. The protein complex cuts a DNA sequence of choice before using a specific template to transcribe an alternative sequence complementary to the template DNA. This directly alters the targeted gene, making it a desirable form of gene regulation. However, the complexity of the procedure and the necessary precision have prevented its widespread use. Despite this, the first patient was just treated with a personalized CRISPR gene therapy to repair an inactive enzyme sequence. 

Drs. Rebecca Ahrens-Nicklas and Kiran Musunuru, who work in the University of Pennsylvania’s Perelman School of Medicine, have been studying the possibility of creating customized gene editing therapies for individuals with metabolic disorders, specifically urea cycle disorders. KJ, a patient at the Children’s Hospital of Pennsylvania (CHOP), is a baby diagnosed with urea cycle disorder, meaning he does not have an essential enzyme needed to convert ammonia to urea. Because of his mutation, toxic amounts of ammonia accumulate in his body, particularly in his liver and brain. Since they were already studying his specific malady, doctors ordered him a genomic test as part of CHOP’s Baby Eagle Program. The program provides a rapid sequence of the baby’s entire genome before analyzing a sample of genes that are known to cause genetic disorders. The results indicated that he has carbamoyl-phosphate synthase 1 deficiency (CPS1) because of the CPS1 gene. Unfortunately, the only cure for this type of deficiency is a liver transplant, which would be rare to obtain because of KJ’s small size and health requirements. Due to the fatal amount of organ damage ammonia build up can cause, it was essential for the hospital to find alternative cures for patients like KJ. 

Drs. Ahrens-Nicklas and Musunuru were already researching how to use gene editing to create customized treatments for these types of deficiencies. In fact, they had been studying similar diseases for years before meeting KJ; thus, they were well equipped to provide him with a treatment. Their team attempted various genetic modifications based on the genes associated with CPS1 to identify the optimal choice for gene editing in KJ specifically. Such research studies take months of trial and error, and in this case, after successful lab results, they developed a therapy for KJ’s specific condition after six months. However, since it was created specifically for him, there were no previous examples to prove that it was viable or safe. After being informed of the unknown and potentially harmful consequences, his parents decided to go along with the treatment due to the severity of KJ’s condition. 

On February 25th, 2025, KJ became the first patient to receive a systemic personalized gene editing drug. The drug was delivered via IV and entered his bloodstream as a highway to the liver. At the cellular level, the drug was packaged in lipid nanoparticles and taken to the nucleus, where the gene editing could occur since this is where DNA is housed and thus where replication is performed. As previously stated, CRISPR works by finding the sequence of choice, in this case, the CPS1 gene, then the Cas9 protein snips it out, replacing it with the provided target sequence made specially for KJ. Thankfully, after the administration of the gene therapy drug, KJ’s ammonia levels dropped to a healthy level. As a result, he was able to consume more protein, reduce his medication intake, and gain weight, demonstrating a successful response to the gene therapy.

Now, with the proof that this type of treatment is viable, researchers can continue analyzing more genes to treat other children. Additionally, this may decrease the length of clinical trials to get more therapies approved by the FDA. Currently, there are only two approved therapies, one for sickle cell anemia and one for beta thalassemia. There are many rare disorders with no cure, but this opens the door for more therapies to be offered. Though we are starting small with this one successful case, this is just the beginning of what CRISPR is capable of, and the coming years will show what new possibilities are now a reality.