Genetic engineering of human pluripotent cells using TALE nucleases

Dirk Hockemeyer; Haoyi Wang; Samira Kiani; Christine S. Lai; Qing Gao; John P. Cassady; Gregory J. Cost; Lei Zhang; Yolanda Santiago; Jeffrey C. Miller; Bryan Zeitler; Jennifer M. Cherone; Xiangdong Meng; Sarah J. Hinkley; Edward J. Rebar; Philip D. Gregory; Fyodor D. Urnov; Rudolf Jaenisch

doi:10.1038/nbt.1927

Genetic engineering of human pluripotent cells using TALE nucleases

Dirk Hockemeyer, Haoyi Wang, Samira Kiani, Christine S. Lai, Qing Gao, John P. Cassady, Gregory J. Cost, Lei Zhang, Yolanda Santiago, Jeffrey C. Miller, Bryan Zeitler, Jennifer M. Cherone, Xiangdong Meng, Sarah J. Hinkley, Edward J. Rebar, Philip D. Gregory, Fyodor D. Urnov, Rudolf Jaenisch

Research output: Contribution to journal › Article › peer-review

982 Scopus citations

Abstract

Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).

Original language	English (US)
Pages (from-to)	731-734
Number of pages	4
Journal	Nature biotechnology
Volume	29
Issue number	8
DOIs	https://doi.org/10.1038/nbt.1927
State	Published - Aug 2011
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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Hockemeyer, D., Wang, H., Kiani, S., Lai, C. S., Gao, Q., Cassady, J. P., Cost, G. J., Zhang, L., Santiago, Y., Miller, J. C., Zeitler, B., Cherone, J. M., Meng, X., Hinkley, S. J., Rebar, E. J., Gregory, P. D., Urnov, F. D., & Jaenisch, R. (2011). Genetic engineering of human pluripotent cells using TALE nucleases. Nature biotechnology, 29(8), 731-734. https://doi.org/10.1038/nbt.1927

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title = "Genetic engineering of human pluripotent cells using TALE nucleases",

abstract = "Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).",

author = "Dirk Hockemeyer and Haoyi Wang and Samira Kiani and Lai, {Christine S.} and Qing Gao and Cassady, {John P.} and Cost, {Gregory J.} and Lei Zhang and Yolanda Santiago and Miller, {Jeffrey C.} and Bryan Zeitler and Cherone, {Jennifer M.} and Xiangdong Meng and Hinkley, {Sarah J.} and Rebar, {Edward J.} and Gregory, {Philip D.} and Urnov, {Fyodor D.} and Rudolf Jaenisch",

note = "Funding Information: is a Merck Fellow of the Life Sciences Research Foundation. R.J. was supported by US National Institutes of Health grants R37-CA084198, RO1-CA087869 and RO1-HD045022 and by a grant from the Howard Hughes Medical Institute.",

year = "2011",

month = aug,

doi = "10.1038/nbt.1927",

language = "English (US)",

volume = "29",

pages = "731--734",

journal = "Nature biotechnology",

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T1 - Genetic engineering of human pluripotent cells using TALE nucleases

AU - Hockemeyer, Dirk

AU - Wang, Haoyi

AU - Kiani, Samira

AU - Lai, Christine S.

AU - Gao, Qing

AU - Cassady, John P.

AU - Cost, Gregory J.

AU - Zhang, Lei

AU - Santiago, Yolanda

AU - Miller, Jeffrey C.

AU - Zeitler, Bryan

AU - Cherone, Jennifer M.

AU - Meng, Xiangdong

AU - Hinkley, Sarah J.

AU - Rebar, Edward J.

AU - Gregory, Philip D.

AU - Urnov, Fyodor D.

AU - Jaenisch, Rudolf

N1 - Funding Information: is a Merck Fellow of the Life Sciences Research Foundation. R.J. was supported by US National Institutes of Health grants R37-CA084198, RO1-CA087869 and RO1-HD045022 and by a grant from the Howard Hughes Medical Institute.

PY - 2011/8

Y1 - 2011/8

N2 - Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).

AB - Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).

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Genetic engineering of human pluripotent cells using TALE nucleases

Abstract

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