Home LiteratureArticle Details
PMID: 21738127 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genetic engineering of human pluripotent cells using TALE nucleases.

Nature biotechnology ·Vol. 29 ·No. 8 ·2011-07-07 ·Pages 731-4

Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R

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).

MeSH Terms
Base Sequence Embryonic Stem Cells/physiology Endonucleases/genetics,metabolism Gene Targeting/methods Genetic Engineering/methods Homeodomain Proteins/genetics Humans Induced Pluripotent Stem Cells/physiology Molecular Sequence Data Myosin-Light-Chain Phosphatase/genetics Octamer Transcription Factor-3/genetics Transcription Factors/genetics,metabolism Zinc Fingers
Chemicals
Homeodomain Proteins Octamer Transcription Factor-3 POU5F1 protein, human Transcription Factors homeobox protein PITX3 Endonucleases Myosin-Light-Chain Phosphatase
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Hockemeyer Dirk
The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Wang Haoyi
Kiani Samira
Lai Christine S
Gao Qing
Cassady John P
Cost Gregory J
Zhang Lei
Santiago Yolanda
Miller Jeffrey C
Zeitler Bryan
Cherone Jennifer M
Meng Xiangdong
Hinkley Sarah J
Rebar Edward J
Gregory Philip D
Urnov Fyodor D
Jaenisch Rudolf
References (15)
15 references, click to expand
  1. Breaking the code of DNA binding specificity of TAL-type III effectors.
    Science. 2009 Dec 11;326(5959):1509-12 PMID: 19933107
  2. Gene targeting in human pluripotent cells.
    Cold Spring Harb Symp Quant Biol. 2010;75:201-9 PMID: 21209393
  3. A TALE nuclease architecture for efficient genome editing.
    Nat Biotechnol. 2011 Feb;29(2):143-8 PMID: 21179091
  4. Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells.
    Cell Stem Cell. 2009 Jul 2;5(1):97-110 PMID: 19540188
  5. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures.
    Nat Methods. 2011 Jan;8(1):74-9 PMID: 21131970
  6. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases.
    Nat Biotechnol. 2009 Sep;27(9):851-7 PMID: 19680244
  7. A simple cipher governs DNA recognition by TAL effectors.
    Science. 2009 Dec 11;326(5959):1501 PMID: 19933106
  8. Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription.
    Nat Biotechnol. 2011 Feb;29(2):149-53 PMID: 21248753
  9. Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations.
    Cell. 2011 Jul 22;146(2):318-31 PMID: 21757228
  10. Homologous recombination in human embryonic stem cells.
    Nat Biotechnol. 2003 Mar;21(3):319-21 PMID: 12577066
  11. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency.
    Cell Stem Cell. 2008 Sep 11;3(3):346-353 PMID: 18786421
  12. Genome editing with engineered zinc finger nucleases.
    Nat Rev Genet. 2010 Sep;11(9):636-46 PMID: 20717154
  13. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting.
    Nucleic Acids Res. 2011 Jul;39(12):e82 PMID: 21493687
  14. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations.
    Cell. 2010 May 28;141(5):872-83 PMID: 20471072
  15. Xanthomonas AvrBs3 family-type III effectors: discovery and function.
    Annu Rev Phytopathol. 2010;48:419-36 PMID: 19400638
Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.1927
Published
2011-07-07
Epub
2011-00-07
Pages
731-4
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC3152587
Subset
IM
Grants
NCI NIH HHS · R01 CA087869-10 · United States
NICHD NIH HHS · R01 HD045022-06 · United States
NCI NIH HHS · R01-CA087869 · United States
Howard Hughes Medical Institute · United States
NICHD NIH HHS · R01-HD045022 · United States
NCI NIH HHS · R37-CA084198 · United States
NCI NIH HHS · R01 CA087869 · United States
NCI NIH HHS · R01 CA084198-13 · United States
NCI NIH HHS · R37 CA084198 · United States
NICHD NIH HHS · R01 HD045022 · United States
NCI NIH HHS · R01 CA084198 · United States
External Links
PubMed source DOI: 10.1038/nbt.1927 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2