These experiments are designed to test whether structural alterations of retroviral envelope glycoproteins can direct virus targeting for tissue-specific gene transfer. One avenue explores the expression of a hybrid envelope gene which encodes for a murine pluripotent colony stimulating factor, interleukin 3 (IL3). Such a virus could then specifically target bone marrow cells expressing the high affinity IL3 receptor (IL3R). A second avenue explores construction of a packaging line specific for CD4-positive lymphocytes to introduce HIV anti-sense vectors. Both packaging lines should then allow tissue-specific viral infection of therapeutic genes in vivo without the attendant risks of marrow transplantation.