Talk Summary:

Genome editing technologies have enabled a wide range scientific applications by permitting user-specifiable genomic modifications. However, most genome editing technologies have been repurposed from naturally occurring enzymes, which did not evolve to be designer tools for installing small or large genetic changes. Our team has sought to overcome the inherent caveats and challenges of these natural enzymes, by pioneering the use of protein engineering approaches to improve the precision, efficacy, and safety of CRISPR-based technologies for both research use and in the context of preclinical studies to treat disease. We are rapidly expanding the ’toolbox’ of enzymes capable of directly correcting single base mutations and those that hold promise to treat wider populations of patients via large sequence insertions (e.g. to programmably deliver a corrective cDNA to a specific region of the genome). I will present recent updates on the use of scalable protein engineering and machine learning methods to build a more comprehensive toolbox of millions of CRISPR-Cas enzymes, and on our efforts to develop new approaches for small and large precision genome modifications to treat human diseases. 

Presenter Biography:
Ben Kleinstiver is an Assistant Professor at in the Center for Genomic Medicine at Mass General Hospital (MGH) and Harvard Medical School (HMS), and is the Kayden-Lambert MGH Research Scholar. Dr. Kleinstiver completed his Honours B.Sc. in Biochemistry at the University of Toronto, his PhD at Western University in Dr. David Edgell’s laboratory, and then completed his postdoctoral fellowship at MGH and Harvard. Some of the research goals in the Kleinstiver lab are to engineer & improve genome editing technologies, to optimize methods to accelerate the development of CRISPR enzymes, and to transform these safer, more effective, and versatile tools into new classes of genetic therapies.

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