Therapeutic Protein Compositions and Methods of Making and Using the Same

A therapeutic composition comprising:

• a protein cluster comprising a plurality of therapeutic protein monomers reversibly cross-linked to one another, wherein the protein cluster has a size between 30 nm and 1000 nm in diameter measured by dynamic light scattering;
• a plurality of biodegradable cross-linkers each having two, three or four functional groups capable of reacting with nucleophilic groups on the therapeutic protein monomers, thereby cross-linking the therapeutic protein monomers into the protein cluster, wherein the cross-linker degrades, after administration into a subject in need thereof, under physiological conditions so as to release the therapeutic protein monomers from the protein cluster;
• a pharmaceutically acceptable carrier or excipient;
• and
• optionally, a surface modification on the protein cluster, wherein preferably the surface modification is polycation.