Luciferin Detection After Intranasal Vector Delivery Is Improved by Intranasal Rather Than Intraperitoneal Luciferin Administration

被引:24
作者
Buckley, Suzanne M. K. [1 ,2 ]
Howe, Steven J. [3 ]
Rahim, Ahad A. [1 ,2 ]
Buning, Hildegard [4 ,5 ]
McIntosh, Jenny [6 ]
Wong, Suet-Ping [7 ]
Baker, Andrew H. [8 ]
Nathwani, Amit [6 ]
Thrasher, Adrian J. [3 ]
Coutelle, Charles [7 ]
Mckay, Tristan R. [9 ]
Waddington, Simon N. [1 ,2 ]
机构
[1] Royal Free & Univ Coll Med Sch, Dept Haematol, Haemophilia Ctr, London NW3 2PF, England
[2] Royal Free & Univ Coll Med Sch, Haemostasis Unit, London NW3 2PF, England
[3] UCL, Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England
[4] Univ Cologne, Clin Internal Med 1, D-50937 Cologne, Germany
[5] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany
[6] UCL, Dept Haematol, London WC1E 6HX, England
[7] Univ London Imperial Coll Sci Technol & Med, Gene Therapy Res Grp, London SW7 2AZ, England
[8] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland
[9] Core Technol Facil, NW Embryon Stem Cell Ctr, Manchester M13 9NT, Lancs, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
D O I
10.1089/hum.2008.023
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In vivo bioimaging of transgenic luciferase in the lung and nose is an expedient method by which to continually measure expression of this marker gene after gene transduction. Its substrate, luciferin, is typically injected into the peritoneal cavity before bioimaging. Here we demonstrate that, compared with intraperitoneal injection, intranasal instillation of luciferin confers approximately an order of magnitude increase in luciferase bioluminescence detection in both lung and nose. This effect was observed after administration of viral vectors based on adenovirus type 5, adeno-associated virus type 8, and gp64-pseudotyped HIV lentivirus and, to a lesser extent, after nonviral polyethylenimine (PEI) -DNA delivery. Detection increased relative to the concentration of luciferin; however, a standard concentration of 15 mg/ml was well beyond the saturation point. Compared with intraperitoneal injection, intranasal instillation yields about a 10-fold increase in sensitivity with an approximate 30-fold reduction in luciferin usage when bioimaging in the nasal and pulmonary airways of mice.
引用
收藏
页码:1050 / 1056
页数:7
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