Benjamin Kleinstiver

Kleinstiver Laboratory

The Kleinstiver laboratory at Massachusetts General Hospital seeks to develop and improve genome editing technologies for biomedical research and clinical applications.

Overview

Genome editing technologies offer hope for the correction of disorders that are the result of mutations in a patient’s DNA. Dr. Kleinstiver's research group pursues protein engineering strategies to improve important properties of CRISPR genome editing nucleases (including their activities, specificities, and targeting ranges), while also exploring the feasibility of applying these engineered technologies for the treatment of genetic diseases.

Dr. Kleinstiver is a Principal Investigator in the Center for Genomic Medicine at the Massachusetts General Hospital (MGH) and Harvard Medical School (HMS).

Research in the Kleinstiver laboratory is supported by an NIH Transition to Independence Award, an ASGCT Career Development Award, and a Landenberger Research Foundation Award.

Lab Members

Benjamin Kleinstiver, PhD
Principal Investigator, Center for Genomic Medicine, Massachusetts General Hospital
Instructor in Pathology, Harvard Medical School


Katie Christie, PhD, is a postdoctoral researcher in the Kleinstiver laboratory. Originally from Ireland, Katie recently moved to Boston to develop genome editing technologies capable of allele specific editing.


Russell Walton is a technician in the Kleinstiver laboratory who has developed several assays to characterize and engineer genome editing proteins. Russell completed his undergraduate degree at UCLA and will attend graduate school in the fall of 2019.


Joey Rissman is a technician in the Kleinstiver laboratory who works on CRISPR-Cas12a enzymes and the development of base editor technologies. Joey completed his undergraduate degree at Northeastern University.

Research Projects

Improving the targeting range and activities of CRISPR genome editing technologies

Some of the major limitations of genome editing enzymes include the inability to target sequences of interest, and suboptimal/inadequate activity at the intended on-target site.

The Kleinstiver laboratory engineers naturally occurring CRISPR nucleases to allow them to target more frequently in the genome, enabling researchers to access previously untargetable sequences.

These engineered Cas9 and Cas12a enzymes have implications for various genome editing applications, including gene knock-out and knock-in, epigenome editing, base editing, and allele specific discrimination.


Defining and minimizing the off-target effects of CRISPR nucleases

Genome editing technologies can exhibit the propensity to target DNA sequences that resemble the intended on-target site.

The recognition and cleavage of ‘off-target’ sites can lead to unwanted consequences for research applications and can have major implications for the therapeutic use of genome editing technologies.

To prevent off-target cutting, the Kleinstiver lab develops high-fidelity nucleases with vastly improved genome-wide specificities, reducing off-target concerns.


Characterizing and developing alternative technologies with enhanced properties

Beyond the prototypical and most commonly used SpCas9 nuclease, there are additional CRISPR enzymes that have distinct properties. The diverse characteristics of these alternate nucleases are potentially advantageous for biomedical research and for the treatment of human diseases.

The Kleinstiver laboratory seeks to characterize the properties of these genome editing technologies in clinically relevant primary cell types, while exploring their use to correct genetic disorders.

Research Positions

The Kleinstiver laboratory is hiring highly motivated and creative scientists that are interested in improving genome editing technologies while developing solutions to inherited genetic diseases. Candidates interested in postdoctoral, graduate student, or technician positions should direct inquiries to Dr. Kleinstiver; please also include a detailed CV and a brief statement of research interests.

Publications

A complete list of Dr. Kleinstiver’s publications can be found here: https://www.ncbi.nlm.nih.gov/pubmed/?term=kleinstiver+benjamin.

Contact Us

Kleinstiver Laboratory

185 Cambridge Street, 5th Floor

Boston, MA, 02114

Phone: 617-714-6057

Email: bkleinstiver [at] mgh.harvard.edu

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