Nature Biotechnology
19, 838 - 842 (2001)
doi:10.1038/nbt0901-838
Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivoPaul N. Reynolds1, Stuart A. Nicklin2, Lioudmila Kaliberova1, Brian G. Boatman1, 3, William E. Grizzle1, Irina V. Balyasnikova4, Andrew H. Baker2, Sergei M. Danilov4
& David T. Curiel11
Division of Human Gene Therapy, Departments of Medicine, Surgery and Pathology, and Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA. 2
Department of Medicine and Therapeutics, University of Glasgow, Glasgow, UK. 3
Division of Cardiology, University of Alabama at Birmingham, Birmingham, AL, USA. 4
Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA.
Correspondence should be addressed to Paul N. Reynolds Paul.Reynolds@ccc.uab.eduThe 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, flt-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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