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.