Optimal transduction of a particular subset of cells in an individual may require targeting of retroviral vectors to a specific cell type. To achieve this goal, we have begun to study the structure-to-function properties of the envelope protein of murine retroviruses (it is the envelope protein which directs the retrovirus to a particular cell type) . Several approaches are being pursued. One analysis centers on a study of chimeric envelope genes containing defined regions of the MMLV ecotropic envelope substituted for the Corresponding 4070A amphotropic envelope regions. Additional studies underway include investigating the properties of chimeric MMLV/AKV ecotropic envelopes, and analysis of the resulting host range potentials of hybrid MCF/xenotropic envelope viruses. Results of these studies may eventually help in the construction of systems for the direct delivery of gene therapy agents to specific cells in vivo.