Potential Rotation Projects

Improving the Precision of CRISPR/Cas9 nucleases for gene therapy applications:

We are working to improve the precision of the CRISPR/Cas9 system to generate nucleases that will cleave at only a single site in the genome.  These engineering efforts focus on increasing the DNA-editing precision of Cas9 and using protein engineering to introduce new properties into the nuclease.  Much of this work is now transitioning to the use of Cas9 (and Cas12a) protein-RNA complexes.  These modified nucleases will then be applied to patient derived cell-culture systems for the targeted repair or inactivation of disease-causing alleles.  With the eventual goal of creating therapeutics for Sickle Cell Disease, beta-Thalassemia, HIV, Limb Girdle Muscular Dystrophy, Hermansky Pudlak Syndrome and other monogenic disorders.

ex vivo genome editing in CD34+ HSPCs:

We are developing improved Cas9 proteins for delivery ex vivo into CD34+ HSPCs for therapeutic application to sickle cell disease and beta-thalassemia. The goal is to modify the hematopoietic stem cells of a patient to complement the loss of function of the beta-globin gene and then return these cells to the patient through an autologous transplant. 

Development of Cys2His2 Zinc fingers proteins (ZFPs) as targeted therapeutics:

We are developing artificial ZFPs for the regulation of target genes to change their gene expression profiles for therapeutic applications.