A groundbreaking breakthrough in gene editing has enabled the development of a customized Crispr treatment for KJ, a baby born with a rare genetic disorder. The innovative therapy, designed by a team at the Children’s Hospital of Philadelphia and Penn Medicine, targets the specific genetic mutation driving KJ’s disease, offering new hope for patients with rare genetic disorders.
KJ Muldoon was born with a potentially fatal genetic disorder known as CPS1 deficiency, which causes a dangerous amount of ammonia to build up in the blood. The disease is rare and affects about half of babies born with it, with about half dying early in life. Current treatment options are limited and often involve a restrictive diet or liver transplantation.
A team at the Children’s Hospital of Philadelphia and Penn Medicine was able to bypass the standard years-long drug development timeline and use Crispr gene editing technology to create a personalized medicine for KJ Muldoon in just six months. Led by Kiran Musunuru, a professor of translational research at the University of Pennsylvania and Children’s Hospital of Philadelphia, the team worked tirelessly to develop a bespoke treatment that would target the specific genetic mutation driving KJ Muldoon‘s disease.
Crispr gene editing technology has the potential to directly address the underlying genetic cause of a disease rather than simply treating symptoms. The approved Crispr therapy, ‘Casgevy‘, is given as a one-time treatment and targets sickle cell disease and beta thalassemia. However, the Philadelphia-led team designed KJ Muldoon‘s therapy to be redosable out of safety concerns, starting with a low dose to ensure there were no adverse effects.
KJ Muldoon‘s case demonstrates that bespoke genetic treatments can be made quickly and used successfully to treat critically ill patients. The treatment was tested for safety in mice and monkeys before being administered to KJ Muldoon, who received his first dose on February 25. The results are impressive, with KJ Muldoon showing significant improvement in just three doses.
While the road ahead is long and challenging, experts believe that Crispr gene editing technology holds great promise for treating a variety of genetic diseases and types of cancer. However, getting the treatment to the right place in the body remains a challenge. The liver is an easy first target because lipid nanoparticles naturally gravitate there, but only some diseases can be treated in this way.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a revolutionary gene editing tool that allows scientists to edit DNA sequences with unprecedented precision.
Developed in 2012, CRISPR uses a small RNA molecule called guide RNA to locate and target specific genes, which are then cut using an enzyme called Cas9.
This enables researchers to modify or delete genes, opening up new possibilities for treating genetic diseases and improving crop yields.
With its high efficiency and specificity, CRISPR has become a game-changer in the field of genetics.
Fyodor Urnov, scientific director at the Innovative Genomics Institute at UC Berkeley, says that KJ Muldoon‘s case demonstrates that bespoke genetic treatments can be made quickly and used successfully to treat critically ill patients. ‘This could have failed in so many ways,’ he says. ‘Nothing was a given.’ The team’s approach is a model for how gene therapy can be developed and used to treat rare diseases.
Kiran Musunuru hopes that someday no rare disease patient will die prematurely from misspellings in their genes, because we’ll be able to correct them. While there is still much work to be done, the breakthrough in KJ Muldoon‘s case offers a beacon of hope for patients with rare genetic disorders.
Kiran Musunuru is a medical doctor and science writer.
He received his M.D. from the University of California, Los Angeles (UCLA) School of Medicine in 1999.
Musunuru has written for various publications, including The Conversation and Forbes.
His writing focuses on explaining complex scientific concepts to non-experts.
He has also co-authored several books on genetics and medicine.
