Identification of mutations in herpes simplex virus envelope glycoproteins that enable or enhance vector retargeting to novel non-HSV receptors
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsJoseph C. Glorioso, III, Hiroaki Uchida, Justus B. Cohen
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Abstract
In one embodiment, the invention provides an HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, where the viral envelope further comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type. In another embodiment, the invention provides an HSV vector comprising (a) a mutant gC and/or gD envelope glycoprotein which comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type; and (b) a mutant envelope glycoprotein other than gD.
Claims15
A mutant HSV vector comprising a modified glycoprotein selected from the group consisting of a modified gB glycoprotein and a modified gH glycoprotein, wherein, when the parental vector is HSV1 K26GFP, the modified glycoprotein comprises a substitution in one or more amino acid residues selected from the group consisting of gB:A549, gB:S668, gH:N753, and gH:A778, or wherein when the parental vector is a homologous HSV vector, the modified glycoprotein comprises a substitution in one or more amino acid residues of the homologous HSV vector selected from amino acids that correlate to gB:A549, gB:S668, gH:N753, and gH:A778 of HSV1 K26GFP wherein the gB:A549 residue correlates to X in KLNPNXIAS (SEQ ID NO:2) of HSV1 K26GFP, the gB:S668 residue correlates to X in ITTVXTFID (SEQ ID NO:3) of HSV1 K26GFP, the gH:N753 residue correlates to X in VDTDXTQQQ (SEQ ID NO:4) of HSV1 K26GFP, and the gH:A778 residue correlates to X in VPSTXLLLF (SEQ ID NO:5) of HSV1 K26GFP;
- and wherein the homologous HSV vector is an HSV-1 or HSV-2 vector, and wherein the mutant HSV exhibits enhanced entry into B78/TMC or B78H1 cells relative to the parental HSV vector.
Dependencies are inferred from the claim text.