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OwnerJ. Keith Joung, Peter Cabeceirasinventors
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Described herein are virus-like particles (VLPs) and minimal human-derived virus-like particles (mhVLPs), comprising a membrane comprising a phospholipid bilayer with one or more human-derived envelope glycoproteins (env) on the external side. Optionally, a biomolecule cargo is disposed in the core of the VLP or mhVLP on the inside of the membrane. Preferably, the mhVLPs do not comprise any exogenous virally derived proteins, e.g., proteins from viral gag, pro, or pol, or other viral proteins that reside inside of enveloped particles (unless the cargo comprises the viral protein(s)). In some embodiments, the mhVLPs do not comprise any human endogenous retroviral (HERV) proteins other than the env (hENV), e.g., do not comprise gag, pol, or pro that was exogenously introduced into producer cells. In some embodiments, the VLPs include a targeting domain, either fused at the N or C terminus or internally into the hENV, or as a separate membrane-anchored targeting domain. Also described are methods of use of the VLPs or mhVLPs for delivery of the biomolecule cargo to cells.
A HERV envelope protein (hENV) comprising a sequence that is at least 95% identical to a sequence as set forth in Tables 1A-C, wherein the hENV comprises one, two, or all three of:
A targeted human endogenous virus-like particle (theVLP) comprising a human endogenous retroviral (HERV) envelope protein (hENV) and a targeting domain, wherein the hENV optionally comprises a truncation of one to 50 amino acids from the C terminus and/or one or more RBD mutations, wherein the targeting domain is (i) fused at the N or C terminus, or inserted internally into the of the hENV, or (ii) is a membrane-anchored targeting domain comprising a targeting domain fused to a transmembrane domain, and
A minimal human virus-like particle (mhVLP), comprising:
A method of producing a theVLP or an mhVLP comprising a cargo, the method comprising:
A cell expressing (i) a human endogenous retroviral (HERV) envelope protein (hENV), wherein the hENV optionally comprises one, two, or all three of a targeting domain at the N or C terminus, or inserted internally into the protein;
Dependencies are inferred from the claim text.