Antibody-directed targeting of retroviral vectors via cell surface antigens

Targeted stable transduction of specific cells is a highly desirable goal f or gene therapy applications. We report an efficient and broadly applicable approach for targeting retroviral vectors to specific cells. We find that the envelope of the alphavirus Sindbis virus can pseudotype human immunodef iciency virus type 1- and murine leukemia virus-based retroviral vectors. W hen modified to contain the Fc-binding domain of protein A, this envelope g ives a significant enhancement in specificity in combination with antibodie s specific for HLA and CD4 relative to that without antibody. Unlike previo us targeting strategies for retroviral transduction, the virus titers are r elatively high and stable and can be further increased by ultracentrifugati on. This study provides proof of principle for a targeting strategy that wo uld be generally useful for many gene therapy applications.