These experiments are designed to test whether structural alterations of retroviral envelope glycoproteins can direct virus targeting for tissue-specific gene transfer. Ecotropic and xenotropic viruses are modified for expression of a hybrid envelope gene which encodes for a murine pluripotent colony stimulating factor, interleukin 3 (IL3). These viruses are further constructed so that the only mechanism to gain entrance into murine cells is through the IL3 receptor, present only on bone marrow cells. Is such specificity of infection targeting can be demonstrated, the psi sequence could be deleted in order to create packaging cell lines which encapsidate (pseudotype) other retroviral vectors within its own mutant envelope proteins but cannot package its own RNA. Such packaging cell lines would then allow in vivo recombinant gene transfer via IL3-pseudotype retroviral infection.
