In a landmark achievement for personalized medicine, researchers at the Children's Hospital of Philadelphia (CHOP) recently developed and delivered the world’s first personalized CRISPR therapy to a newborn diagnosed with a rare and life-threatening urea cycle disorder (UCD). The therapy, tailored to correct a unique mutation in the CPS1 gene, was identified, manufactured, and delivered within just six months. While much attention has rightfully focused on the clinical feat and the patient’s remarkable recovery, this breakthrough also highlights the indispensable contributions of Integrated DNA Technologies (IDT) and Aldevron, two Danaher operating companies whose scientific and manufacturing expertise played a pivotal role in bringing this therapy to life.
The power of partnership in precision medicine
Personalized CRISPR therapies demand rapid development, rigorous quality, and seamless coordination across multiple domains. For the CHOP team, time was the most critical factor, as every day without treatment increased the risk of irreversible neurological damage to the patient. To meet this unprecedented challenge, they collaborated with trusted partners known for their scientific excellence, reliability, and speed: IDT and Aldevron.
IDT synthesized the custom CRISPR guide RNA (gRNA) that enabled the precise correction of a disease-causing mutation in the CPS1 gene; delivering the gRNA quickly and at therapeutic-grade purity, helping ensure the accuracy of the gene editing process.
Beyond synthesis, IDT scientists also supported critical safety assessments by deploying a rapid, multi-method framework for nominating and confirming potential off-target editing sites. The team rapidly constructed and manufactured relevant CRISPR enzymes and mRNAs that were used in safety studies for this project. By integrating in vitro, in silico, and cell-based approaches, they collaborated with CHOP/ University of Pennsylvania and the Innovative Genomics Institute (IGI) to identify off-target sites and confirm a lack of off-target base-editing at over 300 candidate sites, providing CHOP with the data needed to move forward with confidence and do so without compromising the pace of development.
Meanwhile, Aldevron manufactured the mRNA encoding the therapeutic base editor used in the treatment, utilizing CHOP-provided linear template pDNA. This custom mRNA, designed to express a Cas9 variant fused to an adenine base editor (ABE8e), served as the core of the in vivo editing system. Produced under tight timelines and high-quality standards, Aldevron’s mRNA enabled precise correction of the disease-causing mutation in liver cells. Their ability to rapidly manufacture CGMP-grade mRNA tailored specifically for this one-patient application was critical to the therapy’s success. In addition to producing the mRNA payload, Aldevron also manufactured the final drug product, encapsulating the mRNA and gRNA into lipid nanoparticles provided by Acuitas Therapeutics, dispensing the formulation into vials, and performing all necessary analytical testing and QC release, ensuring that the final therapeutic formulation met stringent specifications for safety, potency, and clinical delivery.
IDT and Aldevron also collaborated to create a streamlined framework and worked closely with the FDA. Leveraging their regulatory (QARA) expertise and rigorous documentation, they enabled expedited delivery and FDA acceptance of the EIND application in just five days, well ahead of the typical 30-day timeline. As a result, collaboration between all parties minimized the regulatory burden and allowed the treatment to be delivered 3.5 weeks earlier than scheduled.
Together, these contributions exemplify how integrated partnerships are accelerating the transition from bench to bedside in the age of precision medicine.
Six months from sequence to cure
The CHOP team’s ability to move from genetic diagnosis to treatment delivery in just six months is virtually unprecedented. The peer-reviewed article published in The New England Journal of Medicine details how clinicians identified the mutation in CPS1 gene and successfully used a non-viral CRISPR strategy to correct it first in vitro in liver cells, then in vivo, in a mouse and non-human primate models, and eventually restoring normal metabolic function and dramatically improving the patient’s condition.
This scientific feat was possible only because of a network of trusted partners, each delivering high-quality, time-sensitive components and data under extreme pressure. IDT’s dual contributions in RNA synthesis and off-target analysis, combined with Aldevron’s rapid manufacture of a customized mRNA payload, contributed to the backbone of this therapeutic success story.
A blueprint for the future of personalized gene editing
This case represents more than a single patient’s rescue; it’s a blueprint for what’s possible in the future of genomic and personalized medicine. These efforts are part of a growing movement to make rapid, individualized genome editing accessible to more patients. Danaher–IGI Beacon for CRISPR Cures initiative, a collaborative initiative between the Innovative Genomics Institute and Danaher Corporation (the parent company for IDT and Aldevron) is designed to accelerate the development of N-of-1 gene-editing therapies. The Beacon project seeks to build a scalable, repeatable model for delivering custom CRISPR treatments safely and efficiently. Rather than approaching each rare disease as a standalone challenge, the initiative focuses on creating a shared platform, a “cookbook” of validated tools, workflows, and regulatory strategies that can be adapted to many genetic conditions.
The CHOP story is a powerful reminder that while innovation often begins at the lab bench, it can only change lives when it’s supported by an ecosystem committed to excellence, urgency, and impact. Together with initiatives like the IGI Beacon, we are entering a new era where personalized gene editing is not only possible, it’s within reach.
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