KJ Muldoon (infant) is the first person in the world who received in vivo gene-editing therapy making medical history in 2025. It was made at Children’s Hospital of Philadelphia/Penn Medicine.
KJ was born with a rare metabolic disorder known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a life-threatening metabolic disorder that impairs the body’s ability to clear ammonia.
Genetic Analysis:
Genetic analysis revealed that KJ inherited two distinct truncating (nonsense premature stop) variants in the CPS1 gene: Q335X (it means Glutamine into Stop codon at the site of CDS 335) and E714X (glutamic acid into stop codon at CDS 714). If you want to see the variant details about this mutation, click here:
Gene-Editing Treatment:
A team led by Drs. Rebecca Ahrens-Nicklas and Kiran Musunuru developed a therapy delivered via lipid nanoparticles to the liver that uses a base-editing CRISPR. The first dose was administered in February 2025 (at 6-7 months old) and followed by further escalating doses in March and April (7-8 months old).
Gene-Editing Design
The team chose to target one of the two mutants (rather than both), and selected the Q335X variant for the adenine base editing (A—>G conversion). Maybe this is a good strategy because of off-targets and bystand targets.
Outcome:
Doctors reported that the treatment was successful in correcting the genetic defect and reducing ammonia levels in KJ’s blood. He was able to go home from the hospital in June 2025 and is currently thriving.
We do not know editing efficiency, off-target and by-stand target rate, but saved a life.
For more detailed news, please click here
(biotech news) Personalized CRISPR startup, Aurora, Jan 9 2026
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