Infant with Rare Genetic Disorder Successfully Treated with Customized mRNA-based CRISPR Gene Editing Therapy at CHOP and Penn Medicine

PHILADELPHIA – May 15, 2025 – In a landmark medical achievement, a team at Children’s Hospital of Philadelphia (CHOP) and Penn Medicine has successfully treated an infant with a rare genetic disorder using a customized CRISPR gene editing therapy. The infant, KJ, diagnosed with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare metabolic disease, has become the first patient to receive a personalized CRISPR gene-editing therapy. This case, detailed in The New England Journal of Medicine and presented at the American Society of Gene & Cell Therapy Annual Meeting in New Orleans, offers a potential pathway for adapting gene editing for rare diseases.

CRISPR-based gene editing allows for precise correction of disease-causing variants in the human genome. While gene editing tools have primarily been developed for more common diseases, this research focused on creating a customized therapy for KJ’s specific variant of CPS1, a urea cycle disorder. In these disorders, the body cannot convert ammonia, a byproduct of protein breakdown, into urea for excretion, leading to toxic buildup.

Within six months of identifying KJ’s specific genetic variant, the team designed and manufactured a base editing therapy delivered via lipid nanoparticles to the liver to correct the faulty enzyme. KJ received his first infusion in late February 2025, followed by subsequent doses in March and April 2025. Since treatment, he has tolerated increased dietary protein, requires less nitrogen scavenger medication, and has recovered from common childhood illnesses without ammonia buildup. While long-term monitoring is necessary, initial results are highly promising.

Historically, patients with severe CPS1 deficiency often require a liver transplant, a major procedure that many infants are too young or unstable to undergo. This customized in vivo gene editing therapy offers a potential alternative, addressing the underlying genetic defect.

Central to the success of CRISPR-based therapies is the delivery system. Adeno-associated virus (AAV) serves as a stable, long-term vector capable of delivering CRISPR components directly to target cells. Its low immunogenicity and tissue-targeting versatility make it especially well-suited for in vivo editing applications, offering promise for sustained therapeutic effects in pediatric patients. In contrast, mRNA-based CRISPR systems provide a transient and tightly controlled method of gene editing. By expressing gene-editing tools such as Cas9 and guide RNA for a limited time, mRNA delivery reduces off-target risks and enables reversible intervention—an important consideration in early-stage or dose-limiting clinical studies. Together, AAV and mRNA platforms provide complementary delivery strategies for CRISPR therapies: AAV for durable in vivo correction and mRNA for controlled, short-term expression. These technologies are expanding the possibilities for treating pediatric genetic diseases, bringing precision medicine one step closer to clinical reality.

PackGene supports this evolution by offering advanced AAV-based CRISPR delivery and custom mRNA solutions tailored for gene-editing applications. We offer comprehensive and integrated services to accelerate the development of safe, effective, and scalable AAV and mRNA CRISPR-based research and therapeutics, including:

• Ready-to-Use AAV CRISPR Vectors: Pre-packaged, high-quality off-the-shelf AAV vectors for Cas9 or Cpf1 expression under various promoters (broad-spectrum and tissue-specific), with next-day shipping for stocked items and included quality reports.
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• Expert Consultation & Support: Scientific and technical guidance for all stages of AAV and mRNA-based CRISPR research and therapeutic development.