Engineered virus-like nanoparticle heparin antagonists

Virus nanoparticles provide a self-assembling, reproducible multivalent platform that can be chemically and genetically manipulated for the presentation of a wide array of epitopes. Presented herein are engineered bacteriophage Qβ nanoparticles that function as potent heparin antagonists. Three successful approaches have been used: 1) chemically appending poly-Arg peptides; 2) point mutations to Arg on the virus capsid; 3) incorporation of heparin-binding peptides displayed externally on the virus surface. Each approach generates particles with good heparin antagonist activity with none of the toxic side effects of protamine, the only drug currently FDA-approved for clinical use as a heparin antagonist.