1:00 pm to 2:00 pm
“Engineered Nucleases based Genome Editing for Treating Single Gene Disorders”
There are an estimated 6,000 human single-gene disorders, most of them have no cure. This imposes a significant burden on human health worldwide. The recent advent in engineered nucleases, including zinc finger nuclease (ZFN), TAL effector nuclease (TALEN) and CRISPR/Cas (clustered, regularly interspaced, short palindromic repeats and CRISPR-associated protein) systems provides a powerful tool for precisely modifying the genome, thus revolutionizing the treatment of single-gene disorders. In this talk, I will present recent work in my lab on developing new tools and methods for the design and optimization of engineered nucleases, including SAPTA (Scoring Algorithm for Predicting TALEN Activity), PROGNOS (Predicted Report Of Genome-wide Nuclease Off-target Sites) and COSMID (CRISPR Off-target Sites with Mismatches, Insertions and Deletions), and the efforts in developing a clinically applicable gene correction technology to treat sickle cell disease (SCD), which is the first single-gene disorder with molecular understanding. To treat SCD, we constructed TALENs and CRISPR/Cas9 systems that target specifically to the beta-globin gene, and systematically evaluated their on- and off-target cleavage in different cells. We also quantified the nuclease-induced gene modification rates due to homology-directed repair (HDR) and non-homologous end joining (NHEJ). These studies significantly facilitated our pre-clinical investigation of SCD treatment using animal models. The opportunities and challenges in developing nuclease-based strategies for treating single-gene disorders are discussed. Gang Bao is a pioneer in nanomedicine, molecular imaging, and the emerging area of genome editing. The nanoscale structures and devices engineered in his lab have broad-based applications in basic biological research toward the understanding of underlying causes of disease, as well as in the translation of nano-scale tools for disease diagnostics and treatment, such as targeted drug/gene and cell-based therapies.
Gang Bao is a pioneer in nanomedicine, molecular imaging, and the emerging area of genome editing. The nanoscale structures and devices engineered in his lab have broad-based applications in basic biological research toward the understanding of underlying causes of disease, as well as in the translation of nano-scale tools for disease diagnostics and treatment, such as targeted drug/gene and cell-based therapies.
The NIH-funded Nanomedicine Center for Nucleoprotein Machines that he directs is developing gene correction techniques to address an estimated 6,000 single-gene disorders. Their first target is sickle-cell disease, caused by a single mutation in the beta-globin gene. Bao’s ground breaking work in designing and optimizing engineered nucleases plays an essential role in this nanomedicine center. Using DNA-cutting enzymes, such as CRISPR/Cas9 systems, Transcription Activator-Like Effector Nucleases (TALENs) and Zinc Finger Nucleases (ZFNs), Bao is developing tools for precise gene editing. He has also been developing nanotechnologies for multimodality molecular imaging, sensitive detection of RNA and proteins, and for targeted drug delivery.
Bao is the author of more than 150 refereed publications, two books and four book chapters. He is an elected fellow of the American Institute for Medical and Biological Engineering (2007), of the American Physical Society (2007), of the American Association for the Advancement of Science (2009), and of the American Society of Mechanical Engineers (2009). He has served as a member of the Society of Engineering Science’s Board of Directors (2006-2009).
Hosted by the Ferrara Lab.
When: Friday, Sept 18, 2015 1:00 PM
Where: 1005 GBSF