Genome editing technology is advancing at a breathtaking rate. In particular, programmable nucleases based on the CRISPR/Cas9 system are enabling basic and translational research that holds promise for the development of new therapeutics. MCCB researchers are applying this new technology across a number of different platforms to model and treat human diseases, including cancer. In particular, these new tools provide the possibility for gene correction in cases of congenital human disease. Indeed, collaborative efforts between MCCB researchers and other groups on campus are focused on correction of monogenic disorders, such as Huntington’s Disease and Chronic Granulomatous Disease, as well as the eradication of HIV from latent cellular reservoirs. In these cases, nuclease technology is being coupled with viral delivery systems through collaborations with the UMass Gene Therapy Center and RNA Therapeutics Institute to create gene correction therapies or autologous cell-replacement therapies.
Buttressing these nuclease development efforts is the Mutagenesis Core facility, which is housed in MCCB. This core facility provides UMASS Medical School research groups with access to the latest technologies available for introducing targeted genome alterations in human cells and various model organisms.
Click below to see more about how MCCB researchers apply or develop genome editing in their studies:
The Green lab uses CRISPR/Cas9-mediated genome editing technologies for a variety of applications, including targeted gene knockout, epitope tagging endogenous genes for subsequent genome-wide association or proteomic analysis, and generating endogenous reporter genes for functional screens.
The Lawson Lab uses multiple types of nuclease-based technologies to investigate gene function during vascular development. Together with the Wolfe Lab, they were the first group to generate knockout zebrafish through the use of zinc finger nucleases (ZFN). The Lawson Lab has subsequently used ZFNs to reveal new roles for genes during vascular development. More recent work includes use of both TALENs and CRISPR/cas9 for the purpose of large-scale reverse genetic screening efforts in the zebrafish.
The Wolfe Lab focuses on developing new tools for precise targeted gene editing. Platforms include zinc finger nucleases (ZFNs), transcription activator-like nucleases (TALENs) and the CRISPR/Cas9 system, as well as engineered chimeras incorporating multiple DNA:protein interfaces. Together, these tools are subsequently applied in zebrafish to study gene function or in human cells to develop new therapeutic modalities.