October 15th, 2020 11:00 AM EDT
Correction of the Sickle Cell Disease Mutation with CRISPR/Cas9
Dr. Mark DeWitt
Project Scientist at the University of California, Los Angeles
Sickle Cell Disease (SCD), one of the world’s most common genetic disorders, causes anemia and progressive multiorgan damage that typically shortens lifespan by decades; currently there is no broadly applicable curative therapy. A universal curative therapy for SCD would address a critical unmet medical need in the United States and worldwide. During this webinar, Dr. Mark DeWitt will discuss the development of a CRISPR/Cas9-based strategy to correct the mutation in CD34+ HSPCs harvested from SCD patients. This technique does not rely on viral vectors that can be challenging to manufacture, instead using synthetic reagents: a Cas9 ribonucleoprotein (RNP) targeting the sickle mutation, and a short single-stranded DNA to program gene correction via homology-directed repair (HDR). These studies will be used to support a 2020 IND filing to initiate a Phase I clinical study in 2021, the first of its kind using CRISPR/Cas9-mediated homology-directed repair in hematopoietic stem/progenitor cells. He will conclude with a critical assessment of the current state of sickle cell disease gene therapy, including progress we have made and challenges that still remain.
September 17, 2020 8:00 AM PT
Scalable Manufacturing and Nanovesicle Delivery of CRISPR-Cas9 Ribonucleoproteins Using a cGMP- Compliant Cell Engineering Platform
MaxCyte Field Application Scientist
CRISPR-Cas9 has tremendous potential as a therapeutic tool for treating human diseases. However, prolonged expression of the nuclease and gRNA from viral vectors in an in vivo context may cause unwanted off-target activity and immunogenicity. To overcome these safety issues, a system was recently developed for transient delivery of CRISPR-Cas9 ribonucleoprotein (RNP), recruiting Cas9 protein by chemically-induced dimerization and sgRNA via a viral RNA packaging signal into extracellular nanovesicles. This system, termed NanoMEDIC (nanomembrane-derived extracellular vesicles for the delivery of macromolecular cargo), demonstrates efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells and myoblasts, and also in vivo in a luciferase reporter mouse model.
August 04, 2020 11:00 AM EDT
Flexible, clinically adaptable, non-viral approaches to CAR TCR methodologies
Rama S Shivakumar
Research Scientist and Customer Application Specialist, MaxCyte Inc.
In this webinar for scientists and researchers, Rama Shivakumar, a senior scientist at MaxCyte Inc., will highlight powerful case studies that demonstrate the successful use of MaxCyte’s clinically validated, scalable electroporation system in the pre-clinical and clinical scale engineering of resting and activated T cells using a mesothelin specific CARmRNA; in the enhancement of NK cell cytotoxicities against B cell malignancies using an antiCD19 CAR mRNA; in the transposon (Piggybac and Sleeping Beauty) based gene delivery for manufacture of CAR-T cells ; and finally in the gene editing of T cells for improving the efficacy of a TCR immunotherapy. In particular, during this webinar she will discuss how MaxCyte’s versatile ExPERT platform can enable the next-generation non-viral CAR T therapies including allogeneic, off-the-shelf modalities with the potential for enhanced effectiveness for refractory cancer.