STRATEGIES FOR ACHIEVING MULTIPLE LAYERS OF SELECTIVITY IN GENE-THERAPY

Here we review the progress towards the development of targeted vector s for direct in vivo delivery in gene therapy. Currently, there are ma ny separate approaches, These include: simple physical/anatomical loca lization of administration of the vector at the site where gene transf er is required; exploitation of natural tropisms of plasmid, viral and cellular vectors; and the use of molecular engineering to change the specificity of proteins and nucleic acids so that they specifically re cognize target ligands expressed on/in the target cells. Unfortunately , each of these approaches is usually imperfect by itself. However, co mbinations of these strategies might produce vectors in which several layers of imperfect targeting give an overall level of specificity tha t can justify systemic delivery of vectors to treat human disease.