Correction of the Sickle Cell Disease Mutation with CRISPR/Cas9
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.

Learning Objectives:
Discover a GMP-compliant non-viral gene editing manufacturing protocol to correct the SCD mutation.
Understand the preclinical requirements for a novel CRISPR cell therapy.
Assess the advantages of scalable non-viral approach.

Mark DeWitt received his PhD in Biophysics from the University of California, Berkeley. His post-doctoral work, with Jacob Corn at UC Berkeley was focused on development of a gene correction protocol for sickle cell disease. This work led to TRAN1 and CLIN1 grants from CIRM to develop this protocol into an HSPC cell therapy for sickle cell disease. Dr. DeWitt now manages this project, coordinating teams across UC Berkeley, UCLA, and UCSF.