Viral vectors with modified tropism
AssigneesSelective Genetics, Inc., The University of Birmingham
InventorsBarbara A. Sosnowski, Andrew Baird, Glenn F. Pierce, David T. Curiel, Joanne T. Douglas, Buck E. Rogers
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Abstract
The present invention relates to gene therapy. In particular, therapeutic agents, therapeutic gene products, and compositions are disclosed. Various systems and methods useful in targeting and delivering non-native nucleotide sequences to specific cells are disclosed, wherein virus-antibody-ligand conjugates are used to facilitate targeting and delivery.
Claims45
A tropism-modified adenoviral vector system that specifically targets cells expressing a preselected receptor, comprising:
- an antibody or fragment thereof that binds an adenoviral capsid protein;
- a targeting ligand that binds the preselected receptor;
- and
- an adenovirus containing a nucleic acid molecule that encodes a therapeutic gene product under the control of a promoter;
- wherein the ligand is conjugated to the antibody or fragment thereof and wherein the antibody or fragment thereof is bound to the adenovirus.
A pharmaceutical composition comprising a physiologically acceptable buffer and a tropism-modified adenoviral vector presenting a ligand on its surface, wherein the vector includes a nucleic acid molecule encoding a therapeutic gene product under the control of a promoter.
A method of treating tumors, comprising administering a pharmaceutical composition comprising a physiologically acceptable buffer and a tropism-modified adenoviral vector presenting a ligand on its surface, wherein said vector includes a nucleotide sequence encoding a therapeutic gene product under the control of a promoter, wherein said therapeutic gene product is selected from the group consisting of E-cadherin, BGP, Rb, p53, CDKN2/P16/MTS1, PTEN/MMAC1, APC, p331NG1, Smad4, maspin, VHL, WT1, Men1, NF2, MXI1, and FHIT.
A method of treating ischemia, comprising administering a pharmaceutical composition comprising a physiologically acceptable buffer and a tropism-modified adenoviral vector presenting a ligand on its surface, wherein said vector includes a nucleotide sequence encoding a therapeutic gene product under the control of a promoter, wherein said therapeutic gene product is selected from the group consisting of IGF, TGFβ1, TGF,β2, TGFβ3, HGF, VEGF 121, VEGF 165, FGF1, FGF2, FGF 4, FGF5, PDGF-A, and PDGF-B.
A method of treating connective tissue injury, comprising administering a pharmaceutical composition comprising a physiologically acceptable buffer and a tropism-modified adenoviral vector presenting a ligand on its surface, wherein said vector includes a nucleotide sequence encoding a therapeutic gene product under the control of a promoter, wherein said therapeutic gene product is selected from the group consisting of PTH, BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8, BMP10, BMP11, mammalian BMP, and Xenopus BMP.
A method of treating tissue injury, comprising administering a pharmaceutical composition comprising a physiologically acceptable buffer and a tropism-modified adenoviral vector presenting a ligand on its surface, wherein said vector includes a nucleotide sequence encoding a therapeutic gene product under the control of a promoter, wherein said therapeutic gene product is selected from the group consisting of Bovine VEGF, VEGF, VEGF-B, VEGF-C, Angiopoietin-1, Angiogenin, IGF-1, IGF-II, HGF, PDGF A, PDGF B, TGFB1, TGFB2, and TGFB3.
A method of treating cancer, comprising contacting the cancer cells with a pharmaceutical composition comprising a physiologically acceptable buffer and a tropism-modified adenoviral vector presenting a ligand on its surface,
- wherein said vector includes a nucleotide sequence encoding a therapeutic gene product under the control of a promoter,
- wherein said therapeutic gene product is selected from the group consisting of HSVTK, VZVTK, nitroreductase, and cytosine deaminase;
- and
- contacting the cancer cells with a substrate.
Dependencies are inferred from the claim text.