Selective transduction of protease-rich tumors by matrix-metalloproteinase-targeted retroviral vectors.
We recently showed that retroviral vectors can be targeted through protease substrate interactions. Infectivity is blocked by a polypeptide fused to the viral envelope glycoprotein (SU) and is restored when a protease cleaves the connecting linker, releasing the inhibitory polypeptide from the viral surface. Protease specificity is achieved by engineering the sequence of the linker. Here, using two different matrix-metalloproteinase (MMP)-activatable vectors, we demonstrated highly efficient and selective transduction of MMP-rich target cells in a heterogeneous cell population. In vivo, the MMP-targeted vectors showed strong selectivity for MMP-rich tumor xenografts. Protease-activatable vectors offer new possibilities for in vivo targeting of gene delivery.
Peng
K W
KW
Molecular Medicine Program, Guggenheim 18, Mayo Foundation, Rochester, MN 55905, USA.
Vile
R
R
Cosset
F L
FL
Russell
S
S
D010450:Endopeptidases / Q000378:metabolism*; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D010450:Endopeptidases; D020782:Matrix Metalloproteinases