Specific gene transfer to neurons, endothelial cells and hematopoietic progenitors with lentiviral vectors

被引:120
作者
Anliker, Brigitte [1 ]
Abel, Tobias [1 ]
Kneissl, Sabrina [1 ]
Hlavaty, Juraj [2 ]
Caputi, Antonio [3 ]
Brynza, Julia [1 ]
Schneider, Irene C. [1 ]
Muench, Robert C. [1 ]
Petznek, Helga [2 ]
Kontermann, Roland E. [4 ]
Koehl, Ulrike [5 ]
Johnston, Ian C. D. [6 ]
Keinanen, Kari [7 ]
Mueller, Ulrike C. [8 ]
Hohenadl, Christine [2 ]
Monyer, Hannah [3 ]
Cichutek, Klaus [1 ]
Buchholz, Christian J. [1 ]
机构
[1] Paul Ehrlich Inst, Div Med Biotechnol, D-6070 Langen, Germany
[2] Univ Vet Med, Inst Virol, Dept Pathobiol, Vienna, Austria
[3] Univ Hosp Neurol, Inst Clin Neurobiol, Heidelberg, Germany
[4] Univ Stuttgart, Inst Cell Biol & Immunol, Stuttgart, Germany
[5] Univ Hosp, Frankfurt, Germany
[6] Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
[7] Univ Helsinki, Div Biochem, Dept Biosci, FIN-00014 Helsinki, Finland
[8] Heidelberg Univ, Inst Pharm & Mol Biotechnol, D-6900 Heidelberg, Germany
关键词
TRANSDUCTION; EXPRESSION; DELIVERY; GLYCOPROTEIN; ANTIBODIES; RECEPTORS;
D O I
10.1038/nmeth.1514
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We present a flexible and highly specific targeting method for lentiviral vectors based on single-chain antibodies recognizing cell-surface antigens. We generated lentiviral vectors specific for human CD105(+) endothelial cells, human CD133(+) hematopoietic progenitors and mouse GluA-expressing neurons. Lentiviral vectors specific for CD105 or for CD20 transduced their target cells as efficiently as VSV-G pseudotyped vectors but discriminated between endothelial cells and lymphocytes in mixed cultures. CD133-targeted vectors transduced CD133(+) cultured hematopoietic progenitor cells more efficiently than VSV-G pseudotyped vectors, resulting in stable long-term transduction. Lentiviral vectors targeted to the glutamate receptor subunits GluA2 and GluA4 exhibited more than 94% specificity for neurons in cerebellar cultures and when injected into the adult mouse brain. We observed neuron-specific gene modification upon transfer of the Cre recombinase gene into the hippocampus of reporter mice. This approach allowed targeted gene transfer to many cell types of interest with an unprecedented degree of specificity.
引用
收藏
页码:929 / U93
页数:9
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