Efficient targeted transduction of primary human endothelial cells with dual‐targeted lentiviral vectors

Journal of Gene Medicine - Tập 10 Số 3 - Trang 242-248 - 2008
Nonia Pariente1,2, Si‐Hua Mao1,2, Kouki Morizono1,2, Irvin S. Y. Chen3,1,2
1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
2UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
3Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA

Tóm tắt

AbstractAngiogenesis is a rate‐limiting factor for numerous human diseases. Angiogenic vessels and also the endothelium of certain organs such as the lung display molecular addresses that can be exploited for the selective delivery of gene therapeutics. Lentiviral vectors (LVs) are powerful tools for stable gene delivery but their integration and expression in undesired cell types poses a serious safety concern. We have developed a dual‐targeted LV that can specifically target primary endothelial cells (ECs). Cell selectivity is achieved during entry, using a modified Sindbis virus envelope, and during transcription, with an EC‐specific promoter. We evaluated four surface markers for EC targeting and seven promoter sequences from genes preferentially expressed in ECs. The efficiency and specificity of the double targeted vector were assayed in a panel of human primary cultures and tumor cell lines. A vector targeted to CD146, an endothelial adhesion molecule, and carrying a derivative of the EC tyrosine kinase Tie2 promoter, increased specificity of transduction up to 50 times and was also effective at selectively transducing ECs in a mixed coculture with human fibroblasts. The vector presented here is a potentially powerful tool that could be used in a variety of human diseases. Copyright © 2007 John Wiley & Sons, Ltd.

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Tài liệu tham khảo

10.1042/bst0320397

10.1146/annurev.immunol.18.1.813

10.1172/JCI3008

10.1073/pnas.251662398

10.1038/nature02580

10.1056/NEJM199808133390711

10.1038/35025220

10.1038/35036100

10.1259/bjr/68078705

10.1038/nrc905

10.1038/35025215

Kisker O, 2001, Continuous administration of endostatin by intraperitoneally implanted osmotic pump improves the efficacy and potency of therapy in a mouse xenograft tumor model, Cancer Res, 61, 7669

10.1158/0008-5472.CAN-05-2617

10.1038/sj.cgt.7700938

Check E, 2005, Gene therapy put on hold as third child develops cancer, Nature, 433, 561, 10.1038/433561a

10.1126/science.1088547

10.1007/978-3-642-19012-4_4

10.1128/JVI.75.17.8016-8020.2001

10.1016/j.virol.2006.07.015

10.1038/nm1192

10.1038/sj.mt.6300271

10.1126/science.1067081

10.1161/01.HYP.38.1.65

10.1074/jbc.273.19.11737

10.1128/JVI.78.12.6209-6221.2004

10.1073/pnas.94.7.3058

10.1089/104303403322168028

10.1080/10623320600698037

10.1038/nbt0697-542

10.1016/S0955-0674(03)00100-5

10.1016/S0014-5793(03)00224-2

10.1067/mlc.2001.118519

10.1182/blood-2002-04-1004

10.1038/nbt993

10.1073/pnas.0506938103

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Journal of Gene Medicine

Tập 10 Số 3

242-248

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