Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo

Paul N. Reynolds; Stuart A. Nicklin; Lioudmila Kaliberova; Brian G. Boatman; William E. Grizzle; Irina V. Balyasnikova; Andrew H. Baker; Sergei M. Danilov; David T. Curiel

doi:10.1038/nbt0901-838

Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo

Paul N. Reynolds^*, Stuart A. Nicklin, Lioudmila Kaliberova, Brian G. Boatman, William E. Grizzle, Irina V. Balyasnikova, Andrew H. Baker, Sergei M. Danilov, David T. Curiel

^*Corresponding author for this work

Neurological Surgery

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

216 Scopus citations

Abstract

The promise of gene therapy for health care will not be realized until gene delivery systems are capable of achieving efficient, cell-specific gene delivery in vivo. Here we describe an adenoviral system for achieving cell-specific transgene expression in pulmonary endothelium. The combination of transductional targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE) and an endothelial-specific promoter (for vascular endothelial growth factor receptor type 1, fit-1) resulted in a synergistic, 300,000-fold improvement in the selectivity of transgene expression for lung versus the usual site of vector sequestration, the liver. This combined approach should be useful for the design of other gene delivery systems.

Original language	English (US)
Pages (from-to)	838-842
Number of pages	5
Journal	Nature biotechnology
Volume	19
Issue number	9
DOIs	https://doi.org/10.1038/nbt0901-838
State	Published - 2001

Funding

Acknowledgments This research was supported by grants from the American Heart Association, NIH-NIDDK P30 DK54781, and the Avon Products Foundation to P.N.R.; NIH-NCI RO1 CA74242 to D.T.C. and British Heart Foundation (PG97/018 and PG99/097) grants to A.H.B. We would also like to thank Masato Yamamoto for providing the AdCMVLuc virus, and Long Le, Kathee Mercer, and the UAB Image Analysis Core for technical assistance.

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nbt0901-838

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title = "Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo",

abstract = "The promise of gene therapy for health care will not be realized until gene delivery systems are capable of achieving efficient, cell-specific gene delivery in vivo. Here we describe an adenoviral system for achieving cell-specific transgene expression in pulmonary endothelium. The combination of transductional targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE) and an endothelial-specific promoter (for vascular endothelial growth factor receptor type 1, fit-1) resulted in a synergistic, 300,000-fold improvement in the selectivity of transgene expression for lung versus the usual site of vector sequestration, the liver. This combined approach should be useful for the design of other gene delivery systems.",

author = "Reynolds, {Paul N.} and Nicklin, {Stuart A.} and Lioudmila Kaliberova and Boatman, {Brian G.} and Grizzle, {William E.} and Balyasnikova, {Irina V.} and Baker, {Andrew H.} and Danilov, {Sergei M.} and Curiel, {David T.}",

note = "Funding Information: Acknowledgments This research was supported by grants from the American Heart Association, NIH-NIDDK P30 DK54781, and the Avon Products Foundation to P.N.R.; NIH-NCI RO1 CA74242 to D.T.C. and British Heart Foundation (PG97/018 and PG99/097) grants to A.H.B. We would also like to thank Masato Yamamoto for providing the AdCMVLuc virus, and Long Le, Kathee Mercer, and the UAB Image Analysis Core for technical assistance.",

year = "2001",

doi = "10.1038/nbt0901-838",

language = "English (US)",

volume = "19",

pages = "838--842",

journal = "Nature biotechnology",

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AU - Reynolds, Paul N.

AU - Nicklin, Stuart A.

AU - Kaliberova, Lioudmila

AU - Boatman, Brian G.

AU - Grizzle, William E.

AU - Balyasnikova, Irina V.

AU - Baker, Andrew H.

AU - Danilov, Sergei M.

AU - Curiel, David T.

N1 - Funding Information: Acknowledgments This research was supported by grants from the American Heart Association, NIH-NIDDK P30 DK54781, and the Avon Products Foundation to P.N.R.; NIH-NCI RO1 CA74242 to D.T.C. and British Heart Foundation (PG97/018 and PG99/097) grants to A.H.B. We would also like to thank Masato Yamamoto for providing the AdCMVLuc virus, and Long Le, Kathee Mercer, and the UAB Image Analysis Core for technical assistance.

PY - 2001

Y1 - 2001

N2 - The promise of gene therapy for health care will not be realized until gene delivery systems are capable of achieving efficient, cell-specific gene delivery in vivo. Here we describe an adenoviral system for achieving cell-specific transgene expression in pulmonary endothelium. The combination of transductional targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE) and an endothelial-specific promoter (for vascular endothelial growth factor receptor type 1, fit-1) resulted in a synergistic, 300,000-fold improvement in the selectivity of transgene expression for lung versus the usual site of vector sequestration, the liver. This combined approach should be useful for the design of other gene delivery systems.

AB - The promise of gene therapy for health care will not be realized until gene delivery systems are capable of achieving efficient, cell-specific gene delivery in vivo. Here we describe an adenoviral system for achieving cell-specific transgene expression in pulmonary endothelium. The combination of transductional targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE) and an endothelial-specific promoter (for vascular endothelial growth factor receptor type 1, fit-1) resulted in a synergistic, 300,000-fold improvement in the selectivity of transgene expression for lung versus the usual site of vector sequestration, the liver. This combined approach should be useful for the design of other gene delivery systems.

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JO - Nature biotechnology

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Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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