Construction of retroviral vectors for targeted delivery and expression of therapeutic genes

Current gene therapy protocols take an ex vivo approach in which cells are removed from a patient, genetically modified and then reimplanted. However this kind of approach is both cumbersome and costly, requiring high tech facilities and is limited to cell types that can be easily cultured. The in vivo delivery of genes by retroviral vectors will greatly facilitate gene therapy protocols of the future. However before in vivo gene therapy becomes a reality a number of problems must be overcome. Ideally therapeutic genes should be delivered only to the relevant cell type and/or expressed in this cell type. Strategies are described that (I) limit therapeutic gene delivery, using pseudotyping or vectors based on retroviruses that show a restricted infection spectrum or (II) limit the expression of transferred genes by inclusion of tissue specific promoters or cis acting regulatory elements. The combination of some of these strategies should permit the construction of novel retroviral vectors that provide safe and targeted in vivo gene transfer.