Engineered human-endogenous virus-like particles and methods of use thereof for delivery to cells
AssigneesThe General Hospital Corporation, President and Fellows of Harvard College
InventorsJ. Keith Joung, Peter Cabeceiras
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Abstract
Human-derived virus-like particles (heVLPs), comprising a membrane comprising a phospholipid bilayer with one or more HERV-derived envelope proteins on the external side; one or more HERV-derived GAG proteins in the heVLP core, and a cargo molecule, e.g., a biomolecule and/or chemical cargo molecule, disposed in the core of the heVLP on the inside of the membrane, wherein the heVLP does not comprise a gag protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome, and methods of use thereof for delivery of the cargo molecule to cells.
Claims28
A cell comprising:
- (a) an exogenous nucleic acid molecule that encodes a human endogenous retrovirus (HERV) glycoprotein, and
- (b) an exogenous nucleic acid molecule that encodes a protein comprising a therapeutic cargo fused to a plasma membrane recruitment domain, wherein the plasma membrane recruitment domain is not a viral GAG protein or a CD63 protein.
A composition comprising:
- a nucleic acid molecule that encodes a HERV glycoprotein, and
- a nucleic acid molecule that encodes a protein comprising a therapeutic cargo fused to a plasma membrane recruitment domain, wherein the plasma membrane recruitment domain is not a viral GAG protein or a CD63 protein.
A method of producing a particle that comprises a therapeutic cargo, the method comprising:
- providing a cell comprising:
- (a) an exogenous nucleic acid molecule that encodes a HERV glycoprotein, and
- (b) an exogenous nucleic acid molecule that encodes a protein comprising a therapeutic cargo fused to a plasma membrane recruitment domain, wherein the plasma membrane recruitment domain is not a viral gag protein or a CD63 protein, and
- maintaining the cell under conditions such that the cell produces the particle.
Dependencies are inferred from the claim text.