Chemically activated nanocapsid functionalized for cancer targeting
AssigneeThe Regents of the University of California
InventorsR. Holland Cheng, Li Xing, Chun Chieh Chen, Marie Stark
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Abstract
Modified capsid proteins containing at least a portion of hepatitis E virus (HEV) open reading frame 2 (ORF2) having one or more cysteine residues in a surface variable loop or the C-terminus of HEV ORF2, or a portion thereof, are provided. The modified capsid proteins can be used to form hepatitis E virus (HEV) virus like particles (VLPs) having cysteine functional groups exposed on the outer-surface. The exposed cysteine functional groups can be modified via their thiol reactive group. For example, a bioactive agent, such as a cell-targeting ligand, can be conjugated to the one or more cysteines for targeted delivery of chemically activated nanocapsids.
Claims17
A modified capsid protein comprising a portion of hepatitis E virus (HEV) open Reading Frame 2 (ORF2) protein that is able to form an acid and proteolytically stable HEV virus like particle (VLP), wherein the portion of HEV ORF2 comprises the 452-606 segment of the HEV ORF2 protein of SEQ ID NO:1, 2, 3, 4, 5, or 6, wherein at least one residue Y485, T489, S533, N573, or T586 of the HEV ORF2 protein set forth in SEQ ID NO:1 or one of the corresponding residues of SEQ ID NO:2, 3, 4, 5, or 6 is replaced with a cysteine, which is optionally chemically derivatized.
Dependencies are inferred from the claim text.