DBS drives breakthrough in CRISPR therapy

What does it take to create a first-of-its-kind therapy in a matter of months to try and save a child’s life? As seen recently, it takes expertise, collaboration, dedication—and DBS.

DBS^®, or the Danaher Business System, is a set of tools and methodologies developed and used by Danaher and its businesses to drive continuous improvement through innovation, reducing time to market, shrinking lead times and delivering groundbreaking products and solutions. Each of these abilities were put to the ultimate test in the quest to develop and deploy the world’s first personalized CRISPR therapy for an infant at the Children’s Hospital of Philadelphia (CHOP).

“From the moment we learned about the case, there was a deep commitment and understanding from everyone involved around connecting this infant patient to a potential cure,” said Demaris Mills, Vice President and Group Executive, Genomics Medicine at Danaher. “Our operating companies utilized DBS to remove barriers, act quickly and take smart, calculated risks to compress the schedule.”

A Sum Greater than the Parts

“We were first alerted to this case by our collaborators at the Innovative Genomics Institute,” says Sadik Kassim, CSO of Genomics Medicines at Danaher. “The situation was critical: a child had been diagnosed with neonatal-onset CPS1 deficiency and needed treatment fast.”

This deficiency is a form of urea cycle disorder which renders the body unable to remove ammonia from the bloodstream, often leading to fatal outcomes within just days or weeks after birth. “To help this child, we would have to turn what is typically an 18 to 24-month process to design and manufacture a CRISPR-based therapy into one that was less than six months,” Kassim says. 

“It would push the limits of what was possible, but we believed that with our existing technologies, manufacturing capabilities and collaborations, we could do it.”

“In working with Danaher companies since the launch of the Beacon for CRISPR Cures, I’ve come to appreciate how serious their commitment is to creating an accelerated path to making CRISPR a clinical reality,” said Fyodor Urnov, Professor at UC Berkeley and Director, Technology and Translation at the Innovative Genomics Institute. “I thus suggested to the Penn/CHOP team that they would be excellent partners for this first-of-its-kind journey to treating a child before severe disability sets in.”

Because the patient’s CPS1 deficiency was caused by a point mutation in a gene that detoxifies ammonia, the goal of the therapy was to fix the mutation so that the gene could function normally, providing a potential cure for this disease.

CRISPR-based therapies have three key components. First, the gene editor: an enzyme that is delivered into the patient’s cells that converts one type of DNA base into another. Second, the guide RNA: a molecule that positions the gene editor at the specific site of the genome where it can fix the disease-causing mutation. Third, the delivery vehicle: lipid nanoparticles (LNPs) that are used to package up the editor with the guide RNA and send them to the patient’s liver, where they enter the hepatocytes and carry out their gene editing activities.

Innovation at Work

Creating this sophisticated therapy required the close collaboration of IDT and Aldevron, two Danaher businesses, as well as CHOP and a third company, Acuitas. IDT was responsible for producing the guide RNA, Aldevron the mRNA gene editor, and Acuitas the LNP that carried these payloads. The Aldevron team also produced the final LNP-encapsulated Drug Product while the CHOP team treated and monitored the patient.

“Once we had the teams from CHOP, IDT, Acuitas and Aldevron together, we threw a piece of paper on the wall and started mapping it out, which is classic DBS,” said Mark Wetzel, VP/GM of RNA CDMO Services at Aldevron. “We created the ‘swim lanes,’ we identified the dependencies, we worked out the critical path of what needed to happen by when, and we quickly turned that into an Action Plan.”

“We really keyed into the DBS mindset of focusing on what's possible, not what's blocking our way,” Wetzel continues. “Together as a team, we quickly came up with a path to achieve what was required to support the emergency IND, the efficacy and safety studies and ultimately the drug product.”

“This was a technically challenging project, requiring a new gRNA sequence, new mRNA-encoded base editor, custom safety services and a new LNP formulation, all on a highly compressed timeline,” said Sandy Ottensmann, VP/GM of Gene Writing & Editing at IDT. “We relentlessly prioritized this project and leveraged DBS via Daily Management and Action Plans to drive progress with an ‘all hands on deck’ approach.”

The collaboration was a success — the patient was treated with the CRISPR therapy at just six months of age. “This was a special case. We're so proud to be involved, especially because this couldn’t have been achieved by just any company,” Wetzel continues. “Danaher’s unique portfolio of connected businesses—Aldevron and IDT, in particular—combined with the DBS mindset allowed us to meaningfully accelerate the process of execution.”

The work was presented at the American Society for Cell and Gene Therapy on May 15, 2025 and published in the New England Journal of Medicine. More time is needed to determine the full outcome of the treatment and its durability, but to date, the child is doing well and showing signs of recovery.

Beyond N of 1

An “N of 1” treatment like this is specifically tailored for an individual, but to make a significant impact on disease burden globally, CRISPR must be scaled up.

“We’re just at the beginning of what’s possible,” Ottensmann noted. “This isn’t just about one breakthrough or one patient; it’s about building a platform that can deliver personalized cures on demand, for thousands of diseases that still have no treatment.”

“To deliver this kind of personalized care at scale, we need to invest in turning CRISPR into a platform,” says Kassim. “We often talk about this as creating a CRISPR cookbook, where all of the ingredients and manufacturing processes have been defined so we know how to combine them into a safe and effective treatment. Importantly, we need to work with regulators to approve this cookbook so treatments can reach patients as quickly as possible.”