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TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer

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TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. / Berdien, B; Mock, U; Atanackovic, D; Fehse, B.

In: GENE THER, Vol. 21, 27.03.2014, p. 539–548.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Berdien, B, Mock, U, Atanackovic, D & Fehse, B 2014, 'TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer', GENE THER, vol. 21, pp. 539–548. https://doi.org/10.1038/gt.2014.26

APA

Berdien, B., Mock, U., Atanackovic, D., & Fehse, B. (2014). TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. GENE THER, 21, 539–548. https://doi.org/10.1038/gt.2014.26

Vancouver

Berdien B, Mock U, Atanackovic D, Fehse B. TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. GENE THER. 2014 Mar 27;21:539–548. https://doi.org/10.1038/gt.2014.26

Bibtex

@article{be75ca016549403fb2a7dc0f3bd0e6e8,
title = "TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer",
abstract = "Adoptive immunotherapy with T lymphocytes expressing transgenic T-cell receptors (TCRs) has shown significant clinical efficacy in various malignant diseases. However, concurrent expression of endogenous and transgenic TCRs in one and the same T cell may impair efficacy and cause safety problems owing to mispairings. The most elegant approach to address these issues is the complete shutoff of the endogenous receptor chains by genome editing. To this end, we designed TCR-α and TCR-β-specific pairs of transcription activator-like effector nucleases (TALENs). TALENs were delivered into T cells using an optimized messenger RNA-electroporation protocol. Based thereon, we obtained precise and highly efficient knockout (KO) in Jurkat (TCR-α: 59.7±4.0%, TCR-β: 37.4±7.3%) as well as primary T cells (TCR-α: 58.0±15.0%, TCR-β: 41.0±17.6%). Moreover, a successive KO strategy for the endogenous TCR chains combined with subsequent transduction of the respective chains of an Influenza virus-specific model TCR led to complete reprogramming of T cells with strongly improved expression and functionality of transgenic TCRs. In conclusion, we have developed novel means for the efficient genome editing in primary T lymphocytes.Gene Therapy advance online publication, 27 March 2014; doi:10.1038/gt.2014.26.",
author = "B Berdien and U Mock and D Atanackovic and B Fehse",
year = "2014",
month = mar,
day = "27",
doi = "10.1038/gt.2014.26",
language = "English",
volume = "21",
pages = "539–548",
journal = "GENE THER",
issn = "0969-7128",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer

AU - Berdien, B

AU - Mock, U

AU - Atanackovic, D

AU - Fehse, B

PY - 2014/3/27

Y1 - 2014/3/27

N2 - Adoptive immunotherapy with T lymphocytes expressing transgenic T-cell receptors (TCRs) has shown significant clinical efficacy in various malignant diseases. However, concurrent expression of endogenous and transgenic TCRs in one and the same T cell may impair efficacy and cause safety problems owing to mispairings. The most elegant approach to address these issues is the complete shutoff of the endogenous receptor chains by genome editing. To this end, we designed TCR-α and TCR-β-specific pairs of transcription activator-like effector nucleases (TALENs). TALENs were delivered into T cells using an optimized messenger RNA-electroporation protocol. Based thereon, we obtained precise and highly efficient knockout (KO) in Jurkat (TCR-α: 59.7±4.0%, TCR-β: 37.4±7.3%) as well as primary T cells (TCR-α: 58.0±15.0%, TCR-β: 41.0±17.6%). Moreover, a successive KO strategy for the endogenous TCR chains combined with subsequent transduction of the respective chains of an Influenza virus-specific model TCR led to complete reprogramming of T cells with strongly improved expression and functionality of transgenic TCRs. In conclusion, we have developed novel means for the efficient genome editing in primary T lymphocytes.Gene Therapy advance online publication, 27 March 2014; doi:10.1038/gt.2014.26.

AB - Adoptive immunotherapy with T lymphocytes expressing transgenic T-cell receptors (TCRs) has shown significant clinical efficacy in various malignant diseases. However, concurrent expression of endogenous and transgenic TCRs in one and the same T cell may impair efficacy and cause safety problems owing to mispairings. The most elegant approach to address these issues is the complete shutoff of the endogenous receptor chains by genome editing. To this end, we designed TCR-α and TCR-β-specific pairs of transcription activator-like effector nucleases (TALENs). TALENs were delivered into T cells using an optimized messenger RNA-electroporation protocol. Based thereon, we obtained precise and highly efficient knockout (KO) in Jurkat (TCR-α: 59.7±4.0%, TCR-β: 37.4±7.3%) as well as primary T cells (TCR-α: 58.0±15.0%, TCR-β: 41.0±17.6%). Moreover, a successive KO strategy for the endogenous TCR chains combined with subsequent transduction of the respective chains of an Influenza virus-specific model TCR led to complete reprogramming of T cells with strongly improved expression and functionality of transgenic TCRs. In conclusion, we have developed novel means for the efficient genome editing in primary T lymphocytes.Gene Therapy advance online publication, 27 March 2014; doi:10.1038/gt.2014.26.

U2 - 10.1038/gt.2014.26

DO - 10.1038/gt.2014.26

M3 - SCORING: Journal article

C2 - 24670996

VL - 21

SP - 539

EP - 548

JO - GENE THER

JF - GENE THER

SN - 0969-7128

ER -