MaxCyte Minutes – Nov 2018 – C
Industry News, Maxcyte Science, Updates & Events
CRISPR-Cas9 burst onto the scientific scene with the publication of Feng Zhang’s breakthrough paper in October 2012. Since then, gene therapy has advanced in an unprecedented manner. As is nearly always the case with the maturation of complex and powerful technologies, there have been many exciting wins and a number of serious challenges. So, what is the state of CRISPR-Cas 9?
While we’re still a long way from CRISPR-Cas9 enabled gene therapies treating or curing the multitude of disease states that can be addressed with this technology, very significant progress has been made.
The first clinical trial backed by a U.S. company for a CRISPR-Cas9 enabled therapy launched in September of this year. CRISPR Therapeutics and Vertex Pharmaceuticals collaborated to develop a therapy for the blood disorder β-thalassemia. The trial, according to ClinicalTrials.gov, is a single-arm, open-label, multi-site, single-dose Phase 1/2 study in up to 12 subjects with transfusion-dependent β-thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001. Although the trial is beginning with 12 subjects, it will likely be expanded to 45.
Poster: GMP-compliant, Non-viral CRISPR-mediated Process Correcting the Sickle Cell Disease (SCD) Mutation in SCD Patient CD34+ Cells Achieves 60% Wild Type Adult Hemoglobin Expression in Differentiated Erythrocytes
- Therapeutically-relevant levels of SCD mutation correction are achieved using a non-viral cell engineering approach
- The gene correction procedure resulted in consistent gene correction efficiency
- The achieved level of gene correction leads to ≥90% HbA expression
- The correction rate is believed to be therapeutically beneficial for SCD patients
Tips from our Experts:
Q: Can I transfect ribonucleoproteins (RNPs) rather than plasmids encoding CRISPR-Cas9?
A: MaxCyte’s cell engineering technology is optimized for highly efficient transfection of multiple loading agents into many challenging cell types, including mammalian and insects cell lines, stem cells and primary hematopoietic cells. Optimized electroporation parameters allow any type of macromolecule, including RNPs, to be loaded with nearly 100% efficiency. Gene James Brady Ph.D.editing rates will vary based on guide RNA sequences and other variables unrelated to transfection, but process optimization for CRISPR-Cas9 and other genome modification technologies can be easily achieved by varying a few key experimental parameters, such as electroporation energy and loading agent concentrations.
James Brady, Ph.D.
Vice President, Technical Applications