The introduction of foreign genetic material in living cells is the basis o
f the current protocols of gene therapy. The concept that the de novo synth
esis of a foreign therapeutic protein requires the entrance of the correspo
nding gene into target cells via virus or synthetic vectors is directly inh
erited from experiments on bacterial transduction or transformation. Howeve
r, the difficulties inherent in the penetration and the expression of forei
gn DNA into eucaryotic cells are probably responsible for the low efficienc
y of this therapeutic approach. In this paper, we explore the possibility o
f avoiding these limiting critical steps by expressing the foreign gene on
the surface rather than inside the target cells by the use of mycoplasma, t
he smallest reported living cell. The absence of transfer of genetic inform
ation between this vector and eucaryotic target cells, the sensibility of m
ycoplasmas to antibiotics and their cytadherance are among the interesting
features of this potential vector. The interest of this new vector in the c
ase, e.g. of the gene-directed enzyme prodrug therapy of solid tumors, is d
iscussed.