Peng K W, Vile R, Cosset F L, Russell S
Molecular Medicine Program, Guggenheim 18, Mayo Foundation, Rochester, MN 55905, USA.
Gene Ther. 1999 Sep;6(9):1552-7. doi: 10.1038/sj.gt.3300982.
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.
我们最近发现逆转录病毒载体可通过蛋白酶底物相互作用进行靶向。感染性被融合到病毒包膜糖蛋白（SU）上的多肽所阻断，当蛋白酶切割连接接头时感染性得以恢复，从而将抑制性多肽从病毒表面释放出来。通过设计接头序列可实现蛋白酶特异性。在此，我们使用两种不同的基质金属蛋白酶（MMP）可激活载体，证明了在异质细胞群体中对富含MMP的靶细胞进行高效且选择性的转导。在体内，MMP靶向载体对富含MMP的肿瘤异种移植物表现出很强的选择性。蛋白酶可激活载体为体内基因递送靶向提供了新的可能性。
