Mammalian cells in culture can be modified by gene transfer and these proce
dures are routinely used in experimental biology. Yet, efficient approaches
to modify certain complex cell populations, stem cells ol cells organized
within a tissue are still lacking. The hurdles to gene transfer can be list
ed by describing the pathway of a nucleic acid molecule, from the external
medium towards the cell nucleus where its encoded information will be expre
ssed. The requirements include the necessity to compact the size of the mac
romolecule, to overcome electrostatic repulsion, to cross a series of membr
anes and to establish itself permanently. Viruses have evolved to achieve t
hese goals and understanding their strategies for cell invasion allows to d
esign vectors for gene transfer. Chemicals or biochemicals able to bind DNA
, as well as physical methods inducing changes in the structure of membrane
s can also be useful for gene transfer. The outcome of gene transfer techno
logies and their improvement pave the way to inovative medical applications
and provide powerful tools for exploring the living world.