Benjamin Kleinstiver

Dr. Ben Kleinstiver received his doctoral degree from the Western University. He had completed postdoctoral research at the MGH and HMS. Dr. Ben Kleinstiver is currently a Assistant Investigator, Massachusetts General Hospital (MGH) and Assistant Professor, Harvard Medical School (HMS). They develop genome engineering technologies for research applications and for the treatment of human diseases. They 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. A major goal of our lab is to learn about the challenges that face the effective clinical translation of genome editing technologies. Situated in the Center for Genomic Medicine at Massachusetts General Hospital, his group is collaborating with several other laboratories to leverage novel technologies to both create disease models, and to develop preclinical strategies to correct pathogenic sequences. They're pursuing these efforts with the hope that the promise of genome editing technologies can be realized for the treatment of human diseases.

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The Kleinstiver Lab

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Genome Editing Technologies 0 Protein Engineering 0 Molecular Medicines 0

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Genome editing technologies simplify our ability to rewrite genetic blueprints of life. However, CRISPR-Cas enzymes found in nature can only manipulate a fraction of the genome. To overcome this limitation, new Cas variants have been developed that unlock nearly the entire genome ...Learn More


The Kleinstiver lab is focused on developing new and improved gene-editing technologies. During his presentation, Dr. Kleinstiver discussed protein engineering strategies applied by his team to improve on-target activity, targeting range, and specificity/safety ofCRISPR/Cas9 ...Learn More


  1. Hille LT, Kleinstiver BP. (2021) Plant genome editing branches out. Nature Plants; doi: 10.1038/s41477-020-00840-7, online ahead of print

  2. Neggers JE, Jacquemyn M, Dierckx T, Kleinstiver BP, Thibaut HJ, Daelemans D. (2020) enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9. Molecular Therapy; doi: 10.1016/j.ymthe.2020.09.025, online ahead of print

  3. Schmidts A, Marsh LC, Srivastava AA, Bouffard AA, Boroughs AC, Scarfò I, Larson RC, Bedoya F, Choi BD, Frigault MJ, Bailey SR, Leick MB, Vatsa S, Kann MC, Prew MS, Kleinstiver BP, Joung JK, Maus MV. (2020) Cell-based artificial APCs resistant to lentiviral transduction for efficient generation of CAR-T cells from various cell sources. Journal for ImmunoTherapy of Cancer; doi: 10.1136/jitc-2020-000990, online ahead of print

  4. DeWeirdt PC, Sanson KR, Sangree AK, Murda H, Hanna RE, Feeley MN, Griffith AL, Teng T, Borys SM, Strand C, Joung JK, Kleinstiver BP, Pan X, Huang A, Doench JG. (2020) Optimization of AsCas12a for combinatorial genetic screens in human cells. Nature Biotechnology; doi: 10.1038/s41587-020-0600-6, online ahead of print

  5. Cruz L, György B, Cheah PS, Kleinstiver BP, Eimer WA, Garcia SP, Sharma N, Ozelius LJ, Bragg DC, Joung JK, Norberto de Souza O, Macedo Timmers LFS, Breakefield XO. (2020) Mutant Allele-Specific CRISPR Disruption in DYT1 Dystonia Fibroblasts Restores Cell Function. Molecular Therapy Nucleic Acids; 15(21):1-12

  6. Osuna BA, Karambelkar S, Mahendra C, Christie KA, Garcia B, Davidson AR, Kleinstiver BP, Kilcher S, Bondy-Denomy J. (2020) Listeria Phages Induce Cas9 Degradation to Protect Lysogenic Genomes. Cell Host Microbe; S1931-3128(20):30190-6

  7. Walton RT, Christie KA, Whittaker MN, Kleinstiver BP. (2020) Unconstrained Genome Targeting with near-PAMless Engineered CRISPR-Cas9 Variants. Science; 368(6488):290-6

  8. Mahendra C, Christie KA, Osuna BA, Pinilla-Redondo R, Kleinstiver BP, Bondy-Denomy J. (2020) Broad-spectrum anti-CRISPR proteins facilitate horizontal gene transfer. Nature Microbiology; 5(4):620-629

  9. Breuer CB, Hanlon KS, Natasan JS, Volak A, Meliani A, Mingozzi F, Kleinstiver BP, Moon JJ, Maguire CA. (2020) In Vivo Engineering of Lymphocytes After Systemic Exosome-Associated AAV Delivery. Scientific Reports; 11;10(1):4544

  10. Hanlon KS, Kleinstiver BP, Garcia SP, Zaborowski SP, Volak A, Spirig SE, Muller A, Sousa AA, Tsai SQ, Bengtsson NE, Lööv C, Ingelsson M, Chamberlain JS, Corey DP, Aryee MJ, Joung JK, Breakefield XO, Maguire CA, György B. (2019) High Levels of AAV Vector Integration Into CRISPR-induced DNA Breaks. Nature Communications; 10(1):4439-4449

  11. Anikeeva P, Boyden E, Brangwynne C, Cissé II, Fiehn O, Fromme P, Gingras AC, Greene CS, Heard E, Hell SW, Hillman E, Jensen GJ, Karchin R, Kiessling LL, Kleinstiver BP, Knight R, Kukura P, Lancaster MA, Loman N, Looger L, Lundberg E, Luo Q, Miyawaki A, Myers EW Jr, Nolan GP, Picotti P, Reik W, Sauer M, Shalek AK, Shendure J, Slavov N, Tanay A, Troyanskaya O, van Valen D, Wang HW, Yi C, Yin P, Zernicka-Goetz M, Zhuang. (2019) Voices in Method Development. Nature Methods; 16(10):945–951

  12. György B, Nist-Lund C, Pan B, Asai Y, Karavitaki KD, Kleinstiver BP, Garcia SP, Zaborowski MP, Solanes P, Spataro S, Schneider BL, Joung JK, Géléoc GSG, Holt JR, Corey DP. (2019) Allele-specific Gene Editing Prevents Deafness in a Model of Dominant Progressive Hearing Loss. Nature Medicine; 25(7):1123-1130

  13. Kleinstiver BP**, Sousa AA, Walton RT, Tak YE, Hsu JY, Clement K, Welch MM, Horng JE, Malagon-Lopez J, Scarfò I, Maus MV, Pinello L, Aryee MJ, Joung JK**. (2019) Engineered CRISPR-Cas12a variants with increased activities and improved targeting ranges for gene, epigenetic and base editing. Nature Biotechnology; 37(3):276-282

  14. **co-corresponding authors

  15. Marino ND, Zhang JY, Borges AL, Sousa AA, Leon LM, Rauch BJ, Walton RT, Berry JD, Joung JK, Kleinstiver BP, Bondy-Denomy J. (2018) Discovery of widespread type I and type V CRISPR-Cas inhibitors. Science; 362(6411):240-24

  16. Lee K, Zhang Y, Kleinstiver BP, Guo JA, Aryee MJ, Miller J, Malzahn A, Zarecor S, Lawrence-Dill CJ, Joung JK, Qi Y, Wang K. (2019) Activities and specificities of CRISPR/Cas9 and Cas12a nucleases for targeted mutagenesis in maize. Plant Biotechnology Journal; 17(2):362-372

  17. György B, Lööv C, Zaborowski MP, Takeda S, Kleinstiver BP, Commins C, Kastanenka K, Mu D, Volak A, Giedraitis V, Lannfelt L, Maguire CA, Joung JK, Hyman BT, Breakefield XO, Ingelsson M. (2018) CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer’s Disease. Molecular Therapy Nucleic Acids; 11:429-440

  18. Chowdhury TA, Koceja C, Eisa-Beygi S, Kleinstiver BP, Ku Kumar SN, Lin CW, Li K, Prabhudesai S, Joung JK, Ramchandran R. (2018) Temporal and Spatial Post-Transcriptional Regulation of Zebrafish tie1 mRNA by Long Noncoding RNA During Brain Vascular Assembly. Arteri. Thromb. Vasc. Biol.; 38(7):1562-1575

  19. Li P, Kleinstiver BP, Leon MY, Prew MS, Nararro-Gomez D, Greenwald SH, Pierce EA, Joung JK, Liu Q. (2018) Allele-specific editing of rhodopsin P23H knock-in mice broadens therapeutic potential of CRISPR/Cas for dominant genetic diseases. The CRISPR Journal; 1(1):55-64

  20. Listgarten J, Weinstein M, Kleinstiver BP, Sousa AA, Joung JK, Crawford J, Gao K, Hoang L, Elibol M, Doench JG, Fusi N. (2018) Predicting off-target effects in silico for end-to-end CRISPR guide RNA design. Nature Biomedical Engineering; 2: 38-47

  21. Tak ET, Kleinstiver BP, Nuñez JK, Hsu JY, Horng JE, Gong J, Weissman JS, Joung JK. (2017) Inducible and multiplex gene regulation using CRISPR-Cpf1-based transcription factors. Nature Methods; 14(12):1163-1166


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