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

Research output: Contribution to journalArticle

202 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 languageEnglish
Pages (from-to)838-842
Number of pages5
JournalNature Biotechnology
Volume19
Issue number9
DOIs
StatePublished - Sep 15 2001
Externally publishedYes

Fingerprint Dive into the research topics of 'Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo'. Together they form a unique fingerprint.

  • Cite this

    Reynolds, P. N., Nicklin, S. A., Kaliberova, L., Boatman, B. G., Grizzle, W. E., Balyasnikova, I. V., Baker, A. H., Danilov, S. M., & Curiel, D. T. (2001). Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo. Nature Biotechnology, 19(9), 838-842. https://doi.org/10.1038/nbt0901-838