In vivo cell type-specific gene delivery with retroviral vectors that display single chain antibodies.
Cell type-specific gene delivery will be essential for in vivo gene therapy. Our laboratory has previously developed retroviral vector particles, derived from spleen necrosis virus, SNV, which display the antigen-binding site of an antibody on the viral surface. Such particles infected only human cells in vitro, which expressed a receptor recognized by the antibody. To test cell type-specific gene delivery in vivo, a mouse model system has been developed. Antibiotic resistant human target and non-target cells were injected into the peritoneum of SCID mice. Subsequently, a vector solution containing 106 infectious particles, which display scAs against the human her2neu cell surface protein, was injected. Cells were recovered from the peritoneum, subjected to antibiotic selection, and tested for the expression of a lacZ gene transduced by the retroviral vector. We found that human target cells, which express her2neu, were infected in vivo. However, neither human cells that do not express her2neu, nor normal mouse cells were infected by such viral particles. These data give proof of principle that retroviral vector-mediated, cell type-specific gene delivery can be obtained in vivo.
Jiang
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A
Thomas Jefferson University, Division of Infectious Diseases, Center for Human Virology, The Dorrance H Hamilton Laboratories, 1020 Locust Street, Suite 329, Philadelphia, PA 19107, USA.
Dornburg
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R
D000818:Animals; D000906:Antibodies; D002460:Cell Line; D004285:Dogs; D004352:Drug Resistance, Microbial / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D007763:Lac Operon; D051379:Mice; D016513:Mice, SCID; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics*
D000906:Antibodies; D018719:Erb-b2 Receptor Tyrosine Kinases