Development and Application of Genome Editing Technologies

The Kleinstiver lab develops genome editing technologies for research applications and for the treatment of human diseases. We develop new approaches and methods to engineer genome editing enzymes, to optimize the properties of CRISPR tools, and to add new functionalities to the editor toolbox, all with the ambition of enabling new treatments for disease.

1. Genome Editing Technology Development. Altering the genetic code of life can now be done with relative ease, as researchers can readily modify nucleic acid sequences in living cells and organisms. This capability has been made possible by decades of research and development of genetic engineering technologies. We have a deep interest in building, characterizing, and optimizing new genome editing technologies to further enable their wide application across a variety of scientific disciplines, with a view to be able to make any change at any position to the genome of a cell.
2. Protein Engineering Methods. We develop new molecular engineering approaches to evolve new properties into naturally occurring enzymes. This process ensures that the technologies that we use for genome editing are as efficient, useful, and safe as posible. CRISPR enzymes evolved over millenia to combat bacterial pathogens, not to function at the whim of a scientist. As such, they’re not equipped with all of the designer characteristics that we want & need for genome editing. To close this gap, we use molecular evolution systems to impart desirable properties into CRIPSR nucleases, with the hope of developing more robust, specific, and broadly targetable technologies. We also develop approaches to scalably characterize the biochemical properties of these enzymes, to be able to build large datasets about their features.
3. Molecular Medicines. A major goal of our lab is to learn about and solve the challenges that face the effective clinical translation of genome editing technologies. How can we take enzymes that evolved in nature and turn them into highly specialized genetic scalpels? Situated in the Center for Genomic Medicine at Massachusetts General Hospital, our group is collaborating with several other laboratories to leverage novel technologies to both create disease models and to develop preclinical strategies to correct pathogenic mutations. We’re pursuing these efforts with the hope that the promise of genome editing technologies can be broadly realized for the treatment of human diseases.