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AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsJoseph C. Glorioso, III, Hiroaki Uchida, Justus B. Cohen
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The invention provides modified HSV vectors that exhibit enhanced entry of cells, either through direct infection and/or lateral spread. In one aspect, HSV vectors of the present invention can directly infect cells through interaction with cell proteins other than typical mediators of HSV infection. In another aspect, the invention provides an HSV vector, which exhibits lateral spread in cells typically resistant to HSV lateral spread, such as cells lacking gD receptors. The invention further provides DNA encoding mutant forms of the HSV gB and gH glycoproteins, stocks of the inventive virus, and methods for effecting viral targeting and efficient entry of cells. The invention also pertains to the use of the inventive vectors for treating cancers.
An HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, wherein the mutations in the glycoproteins are substitution mutations in at least two residues, wherein, when the vector is HSV-1 K26GFP, the at least two residues are selected from the group consisting of gB:D285, gB:A549, gB:S668, gH:N753, and gH:A778, or wherein when the vector is a homologous HSV, the at least two residues are selected from amino acids that correlate to gB:D285, gB:A549, gB:S668, gH:N753, and gH:A778 wherein the gB:D285 residue correlates to X in VYPYXEFVL (SEQ ID NO:1), the gB:A549 residue correlates to X in KLNPNXIAS (SEQ ID NO:2), the gB:S668 residue correlates to X in ITTVXTFID (SEQ ID NO:3) the gH:N753 residue correlates to X in VDTDXTQQQ (SEQ ID NO:4), and the gH:A778 residue correlates to X in VPSTXLLLF (SEQ ID NO:5);
Dependencies are inferred from the claim text.