October 15th, 2020 11:00 AM EDT

Correction of the Sickle Cell Disease Mutation with CRISPR/Cas9

ABSTRACT
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

ABSTRACT
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

ABSTRACT
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.