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AssigneeMassachusetts Institute of Technology
InventorsKarl Dane Wittrup, Christopher Michael Pirie, David Victor Liu, Nicole Jie Yeon Yang
Estimating the term…
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.
A composition for delivery of a therapeutic agent to the cytoplasm of a cell comprising a fusion protein comprising
A composition for delivery of a therapeutic agent to the cytoplasm of a cell comprising a fusion protein comprising
A composition of any of the preceding claims further comprising a therapeutic agent.
A 10th type III fibronectin (Fn3) domain that specifically binds perfringolysin (PFO) and inhibits the activity of PFO, wherein the Fn3 domain comprises BC, DE and FG loops and framework region residues as set forth in Table 1 and Table 2.
Dependencies are inferred from the claim text.