Nilson B H, Morling F J, Cosset F L, Russell S J
Cambridge Centre for Protein Engineering, MRC Centre, UK.
Gene Ther. 1996 Apr;3(4):280-6.
Targetable, injectable vectors would greatly facilitate the development of in vivo therapy strategies. Viral and nonviral vectors can be targeted through ligand-receptor interactions, but protease-substrate interactions have not previously been exploited for vector targeting. Epidermal growth factor (EGF) was fused to a retroviral envelope glycoprotein via a cleavable linker comprising a factor Xa protease recognition signal. Vector particles displaying the cleavable EGF domain could bind to EGF receptors on human cells but did not transfer their genes until they were cleaved by factor Xa protease, whereupon gene delivery proceeded normally. Proteolytic activation of receptor-targeted vectors can therefore provide the basis for a novel two-step targeting strategy that may facilitate efficient targeted in vivo delivery of therapeutic genes.
可靶向的注射型载体将极大地促进体内治疗策略的发展。病毒和非病毒载体可通过配体-受体相互作用实现靶向，但蛋白酶-底物相互作用此前尚未用于载体靶向。表皮生长因子（EGF）通过包含凝血因子Xa蛋白酶识别信号的可裂解接头与逆转录病毒包膜糖蛋白融合。展示可裂解EGF结构域的载体颗粒可与人细胞上的EGF受体结合，但在被凝血因子Xa蛋白酶裂解之前不会转移其基因，裂解后基因传递则正常进行。因此，受体靶向载体的蛋白水解激活可为一种新型两步靶向策略提供基础，该策略可能有助于在体内高效靶向递送治疗性基因。
