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, deri ved from spleen necrosis virus, SNV, which display the antigen-binding site of an antibody on the viral surface. Such particles infected only human ce lls in vitro, which expressed a receptor recognized by the antibody. To tes t cell type-specific gene delivery in vivo, a mouse model system has been d eveloped Antibiotic resistant human target and non-target cells were inject ed into the peritoneum of SCID mice. Subsequently, a vector solution contai ning 10(6) infectious particles, which display scAs against the human her2n eu cell surface protein, was injected. Cells were recovered from the perito neum, 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 v ector-mediated. cell type-specific gene delivery can be obtained in vivo.