Hepadnavirus capsid protein heterodimers and virus-like particles
AssigneeThe Trustees of Indiana University
InventorsZhongchao Zhao, Adam Zlotnick
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Abstract
Embodiments described herein provide orthohepadnavirus capsid protein (Cp) heterodimers, bicistronic vectors encoding the heterodimers, and methods for producing the heterodimers. The heterodimers can be used to form mosaic virus-like particles. In certain embodiments, the heterodimers can form a hexamer, which in turn can be used to nucleate capsid formation, resulting in a Janus particle-like virus-like particle. The hexamer's can then be removed, leaving holey capsids. The capsids can be loaded with, for example, one or more polypeptides, small molecules, or a combination of polypeptides and small molecules. The holes of the holey capsids can be filled with another orthohepadnavirus heterodimer or a homodimer.
Claims15
An orthohepadnavirus capsid protein (Cp) heterodimer, comprising
- i) a first half-dimer comprising an orthohepadnavirus Cp, and
- ii) a second half-dimer comprising an orthohepadnavirus Cp, wherein the first half-dimer and the second half-dimer are not identical, wherein the first half-dimer and the second half-dimer are not linked by a peptide linker,
- wherein the orthohepadnavirus Cp is hepatitis B virus (HBV) Cp,
- wherein the HBV Cp comprises an assembly domain (Cp149) comprising SEQ ID NO:8,
- wherein at least one of the first half-dimer and the second half-dimer has a capsid assembly defect,
- wherein the capsid assembly defect comprises the HBV Cp149 comprising at least one amino acid substitution in SEQ ID NO:8,
- wherein the substituted HBV Cp149 is selected from HBV Cp149-S106A, HBV Cp149-G123A, HBV Cp149-V124A, HBV Cp149-V124C, HBV Cp149-T128A, and HBV Cp149-Y132A, and
- wherein the first half-dimer and the second half-dimer spontaneously dimerize with one another.
Dependencies are inferred from the claim text.