Karl Dane Wittrup,Christopher Michael Pirie,David Victor Liu,Nicole Jie Yeon Yang
申请号：
US14406803
公开号：
US20150174265A1
申请日:
2013.06.26
申请国别(地区):
US
年份:
2015
代理人:
摘要：
The present invention features compositions and methods for enhancing endosomal escape of therapeutic agents in the cytoplasm of a cell to thereby provide more effective therapy. The endocytic pathway is the major uptake mechanism of cells, and biological agents such as proteins, DNA, and siRNA become entrapped in endosomes and subsequently degraded by lysosomal enzymes. The present invention facilitates endosomal escape by providing fusion proteins with membrane disruptive activity. In some embodiments, the fusion protein has endosomolytic activity that is activated at endosomal or lysosomal pH. In other embodiments, the fusion protein has reversible and pH sensitive membrane disruptive activity so that once internalized into the endosomal or lysosomal compartments, the resulting reduction in pH causes the pH sensitive fusion protein to activate and disrupt the endosomal or lysosomal membrane.
