BBS Faculty Member - Benjamin Kleinstiver

Benjamin Kleinstiver

Assistant Professor

Massachusetts General Hospital
Richard B. Simches Research Building (CPZN), Room 5.320
185 Cambridge Street
Boston, MA 02114
Tel: 617-726-6844
Fax: 617-726-5735
Email: BKLEINSTIVER@mgh.harvard.edu
Visit my lab page here and here.



The ability to precisely and permanently alter DNA sequences in living cells has been dramatically simplified by the adaptation of a prokaryotic immune system, CRISPR, for genome editing. The discovery that much of the targeting specificity of CRISPR-associated (Cas) endonucleases could be reprogrammed with a guide RNA fundamentally changed the scope and scale of genome editing experiments. Despite this promise, certain notable properties of Cas enzymes were found to be suboptimal in terms of their safety and activity. Dr. Kleinstiver’s research has addressed major limitations of Cas enzymes, by: (1) expanding their targeting range within genomes to broaden their utility (Kleinstiver et al., Nature 2015; Kleinstiver et al., Nature Biotechnology 2015 & 2019), (2) improving their genome-wide specificities to eliminate undesirable off-target effects (Kleinstiver & Pattanayak et al., Nature 2016; Chen, Dadgas, Kleinstiver et al., Nature 2017), and (3) characterizing and engineering alternative CRISPR nucleases that possess unique desirable properties (Kleinstiver & Tsai et al., Nature Biotechnology 2017; Kleinstiver et al. Nature Biotechnology 2019). These combined innovations enhance the utility and safety of CRISPR nucleases, improving the prospect of their use for both research and clinical interventions.

Notwithstanding these advances, several challenges remain for CRISPR nucleases to be broadly useful for interrogating and correcting disease-relevant sequences. Notably, Cas enzymes remain unable to efficiently discriminate intended from unintended sequences that differ by small sequence changes, and the intended ‘edit-outcome’ is often not achievable at requisite frequencies. The central focus of the Kleinstiver laboratory is therefore to leverage naturally occurring and engineered CRISPR enzymes to more effectively model and treat disease, by:

1) Engineering CRISPR enzymes capable of single nucleotide discrimination
2) Tailoring genome editing reagents for the detection and correction of unique genetic sequences
3) Developing protein engineering strategies to further improve properties of genome editing enzymes
The Kleinstiver laboratory seeks to address important research questions at the forefront of the genome editing field, while also emphasizing mentorship and career development of trainees. For additional details on the broad interests of the Kleinstiver lab, please visit: https://www.kleinstiverlab.org



Last Update: 8/2/2019



Publications

For a complete listing of publications click here.

 


 



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