Aldevron, Jennifer Doudna, and Innovative Genomics Institute Collaborate on In Vivo CRISPR Therapies for Neurologic Diseases. Resulting paper published in Molecular Therapy.

August 29, 2023 / by Aldevron

FARGO, N.D. (August 29, 2023)

Aldevron, a leading global manufacturer of DNA, RNA and proteins used in cell and gene therapies and vaccine development, contributed to a publication in collaboration with 2020 Nobel Laureate Jennifer Doudna and the Innovative Genomics Institute (IGI) at the University of California, Berkeley to advance research on in vivo, CRISPR-based genome editing strategies to address genetic diseases of the central nervous system such as Huntington’s disease and ALS. Aldevron supplied custom CRISPR protein with ultra-low endotoxin, enabling direct delivery to the brain in mice. This partnership resulted in a paper, titled “Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs,” published in the journal Molecular Therapy, the official journal of the American Society of Gene and Cell Therapy.

Along with the research scientists from UC Berkeley, four Aldevron scientists and staff co-authored the paper, which demonstrated that Aldevron’s highly pure Cas9 proteins enable optimization of IGI’s promising therapeutic approach to directly inject CRISPR ribonucleoprotein (RNP) to the brain using a convection-enhanced delivery system. The brain is protected by the blood-brain barrier, which prevents the application of ex vivo CRISPR cell therapy techniques. Delivery of CRISPR tools via traditional in vivo gene therapy vectors such as adeno-associated virus (AAV) has shown promise, but also raises concerns around immunogenicity, packaging capacity and cost.

“We are proud to be part of the interdisciplinary team of biomedical scientists and clinicians in a bold, interwoven effort to use CRISPR-based genome editing to advance therapeutic strategies towards CNS disease,” said Tom Foti, General Manager of the

Protein Business Unit for Aldevron. “By applying Aldevron-developed manufacturing methods to supply the cell-penetrating SpCas9 with ultra-low endotoxin, we were able to support this promising initiative.”

Aldevron supplied the SpCas9 nuclease protein used to dose neurons in in vivo and in vitro mouse experiments. By applying robust industrial process control, Aldevron scientists were able to deliver a pure protein solution that could be delivered in higher concentration to the brain.

“Projects like this show the power of collaborations between academia and industry to accelerate important research,” said Jennifer Doudna, who founded the IGI in 2014. “The IGI’s vision is that CRISPR-based cures can have a real-world impact at scale, and we are pleased to be making much needed advancements in our ability to treat neurologic diseases that affect people worldwide safely and affordably.”

The ability to deliver CRISPR-based therapies to the brain opens the door to a wide variety of possible new treatments for neurologic diseases, including many unaddressed rare diseases.

“Delivering CRISPR cures safely to the brain is fantastic. Applying this to not one but a whole list of neurological diseases is even better,” said Fyodor Urnov, Director of Technology & Translation at the IGI. “While virus-based paths to neuro cures are important, the new paper showcases the clear promise for nonviral delivery of CRISPR-Cas to the brain. In my opinion, this is intrinsically a more scalable technology to address rare neurologic disease using genome editing.”

About Aldevron

Aldevron is a premier manufacturing partner, producing high-quality plasmid DNA, mRNA, proteins, and other key components for the development of vaccines, gene and cell therapies, immunotherapies, and molecular diagnostics. Headquartered in Fargo, North Dakota, with additional locations in Madison, Wisconsin, and Lincoln, Nebraska, Aldevron supports scientists who are developing revolutionary, lifesaving treatments for millions of people. To learn more about how Aldevron is advancing biological science, visit https://www.aldevron.com