As a Project Scientist for the University of California, Los Angeles, Dr. Mark DeWitt has developed a phase 1 GMP-compatible protocol for correcting diseases that cause gene mutations using a CRISPR-Cas9 modular, non-viral gene editing platform. His specific research focuses on a treatment for sickle cell anemia that is more accessible and less costly than a bone marrow transplant—currently, the only way to address the disease.
Over the past year, DeWitt has partnered with Aldevron and Synthego, industry leaders in CRISPR-Cas9 nucleases and gRNA manufacturing, respectively.
DeWitt presented his work in a September 2020 webinar titled “The Future of CRISPR Cell Therapies is GMP” and hosted by Dr. Jeffrey Buguliskis, the technical editor at Genetic Engineering & Biotechnology News (GEN). Tom Foti, president of Aldevron’s Protein Business Unit, and Dr. Robert Deans, Chief Scientific Officer at Synthego, spoke about their companies’ roles in supporting the project.
Aldevron manufactures the necessary Cas9 and complexes it with gRNA produced by Synthego to create an RNP. Aldevron also applies its internally developed testing panel to determine the suitability of the Cas9-gRNA complex. Both companies work with researchers from bench to bedside on CRISPR-enabled gene therapies and vaccines, which provides a significant advantage in the highly competitive field.
Deans said DeWitt’s research demonstrates the ability to use machine learning and automated experimental approaches to improve editing efficiency.
“We’re all quite aware of the high cost of goods associated with lentiviral manufacturing and the limited contract manufacturing capabilities,” he said. “CRISPR is a glimmer of hope for being able to give us a cost-effective, more immediately accessible therapeutic out into the gene medicine space.”
Foti explained that Aldevron makes cGMP RNP with any nuclease or guide and discussed the steps involved:
- Testing panel creation
- RNP Complex optimization
- Free Cas9 measurement
- Free gRNA measurement
- Determination of long-term stability
“The whole idea here is to be able to offer our research-grade solution, and then, when you get into phase 1 you can use GMP source, and when you move to pivotal or commercial grade, you have a GMP solution, all with the same vendor,” he said.
To learn more about DeWitt’s research and the potential of CRISPR-Cas9 genome editing advancing to GMP, watch the webinar.
About the presenters
Mark DeWitt, PhD
|Dr. DeWitt is the scientific project manager at UCLA who is leading an effort to develop a CRISPR-based cell therapy for sickle cell disease, which is now in Investigational New Drug (IND)-enabling phase. He coordinates chemistry, manufacturing and control (CMC) development, in vitro preclinical studies, toxicology and regulatory.
Prior to joining UCLA in 2019, DeWitt was the director of research and development at CellFE - Cell Fluidics Engineering, a project scientist at the Innovative Genomics Institute and a postdoctoral researcher at the University of California, Berkeley.
DeWitt earned his doctorate in biophysics at UC Berkeley and a Bachelor of Arts in biochemistry and microbiology from Reed College, Portland.
Robert Deans, PhD
|Deans has more than 25 years of experience in adult stem cell therapeutics, which includes commercialization of cell therapeutics from bone marrow. This includes both hematopoietic gene therapies as well as mesenchymal stromal cell (MSC) products (Prochymal, MultiStem).
Before joining Synthego, Deans was Chief of Innovation at BlueRock Therapeutics, a biotechnology company that creates allogeneic cell therapeutics by harnessing pluripotent stem cell biology and gene editing tools. Prior to that, he was developing a platform of novel enucleated cell therapeutics based on genetic engineering and expansion of hematopoietic progenitors to mature reticulocytes as the CSO at Rubius Therapeutics.
Deans earned his doctorate at the University of Michigan, Ann Arbor, and a bachelor’s degree in molecular biology from the Massachusetts Institute of Technology, Cambridge, Mass.
|Tom Foti has been leading Aldevron’s Protein Business Unit as president since 2019. He also was one of the founders of the company’s protein development and manufacturing operation, which launched in Madison, Wis., in 2010.
He has been instrumental in developing the complete offering of CRISPR-associate nucleases at Aldevron. Form off-the-shelf products to GMP custom manufacturing, he and his team have helped clients advance their programs from concept to the clinic. Tom also has been at the forefront of providing ribonucleoprotein (RNP) services.
Foti brings more than 25 years of biotechnology experience to collaborating with Aldevron clients. Prior to joining the company, he served in several roles in Merck KGaA’s Bioscience Division, most recently as director of its Global Custom Services business. He started his career in 1992 with Novagen, Inc., serving in manufacturing and operational roles until 1999.
Foti holds a master’s in business administration from Edgewood College, Madison, Wis., and a management leadership certificate from Massachusetts Institute of Technology, Cambridge, Mass. He played college basketball while earning a bachelor’s degree in biotechnology and microbiology from North Dakota State University, Fargo, N.D.