Scot A. Wolfe, Ph.D.
|Ph.D, 1996, Chemistry, Harvard, Boston, MA|
|Postdoctoral research: Massachusetts Institute of Technology, Boston, MA|
|Office:||University of Massachusetts Medical School
364 Plantation Street, LRB-619
Worcester, MA 01605
My research program is focused on the creation of improved genome editing technologies to facilitate both efficient and precise editing of vertebrate genomes. These improved nuclease technologies are being utilized in four areas of study: (1) developing reagents for precise gene correction/replacement that will be utilized for the gene therapy-based correction of monogenic diseases or the inactivation of integrated retroviral genomes; (2) developing therapeutic nuclease-based reagents for a number of diseases including beta-thalassemia, sickle cell disease, chronic granulomatous disease, limb girdle muscular dystrophy and HIV; (3) developing Cys2His2 zinc finger protein reagents for gene therapy applications, and (4) improving reagents for the study of gene function in model organisms with a particular focus on zebrafish.
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 Cpf1) 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, HIV, Chronic Granulomatous Disease, Limb Girdle Muscular Dystrophy 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 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.
Creation of CRISPR/Cas9-based tools for zebrafish:
We are developing CRISPR/Cas9 systems for spatial and temporally restricted editing or gene regulation in zebrafish. These tools will be used to determine the tissue- or cell-type specific function of target genes during development.
A position is available to develop new delivery reagents/methods for CAS9-based nucleases for somatic cell genome editing in collaboration with the Khvorova, Sontheimer and Watts labs. This project is associated with the NIH Common Fund Somatic Cell Genome Editing.
A technician position is available to participate in our gene editing efforts.