We recently showed that retroviral vectors can be targeted matrix-metalloproteinase (MMP)-activatable vectors, we through protease substrate interactions. Infectivity is demonstrated highly efficient and selective transduction of blocked by a polypeptide fused to the viral envelope glyco-MMP-rich target cells in a heterogeneous cell population. protein (SU) and is restored when a protease cleaves the In vivo, the MMP-targeted vectors showed strong selecconnecting linker, releasing the inhibitory polypeptide from tivity for MMP-rich tumor xenografts. Protease-activatable the viral surface. Protease specificity is achieved by enginvectors offer new possibilities for in vivo targeting of eering the sequence of the linker. Here, using two different gene delivery.