Vectors and methods for gene transfer to cells
First Claim
1. A chimeric adenovirus coat protein comprising a nonnative amino acid sequence, wherein said chimeric adenovirus coat protein directs entry into cells of a vector comprising said chimeric adenovirus coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than said chimeric adenovirus protein, and wherein said chimeric adenovirus coat protein binds a novel endogenous binding site present on the cell surface.
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Abstract
The present invention provides a chimeric adenovirus coat protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence. Such a chimeric adenovirus coat protein according to the invention is able to direct entry into cells of a vector comprising the coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than the chimeric adenovirus coat protein. The chimeric coat protein preferably is a fiber, hexon, or penton protein. The present invention also provides an adenoviral vector that comprises the chimeric adenovirus coat protein, as well as methods of constructing and using such a vector.
99 Citations
62 Claims
- 1. A chimeric adenovirus coat protein comprising a nonnative amino acid sequence, wherein said chimeric adenovirus coat protein directs entry into cells of a vector comprising said chimeric adenovirus coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than said chimeric adenovirus protein, and wherein said chimeric adenovirus coat protein binds a novel endogenous binding site present on the cell surface.
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10. A chimeric adenovirus fiber protein comprising a nonnative amino acid sequence, wherein said chimeric adenovirus fiber protein directs entry into cells of a vector comprising said chimeric adenovirus fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than said chimeric adenovirus fiber protein, and wherein said fiber protein comprises a sequence selected from the group consisting of SEQ ID NO:
- 4 and SEQ ID NO;
5, and wherein the length of the polylysine string can vary from about 3 to about 30 residues.
- 4 and SEQ ID NO;
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19. An isolated and purified nucleic acid comprising a sequence selected from the group consisting of SEQ ID NO:
- 7, and SEQ ID NO;
8, and conservatively modified variants thereof.
- 7, and SEQ ID NO;
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28. The adenoviral vector GV10 UTV.
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31. A vector that comprises or encodes a chimeric adenovirus coat protein comprising a nonnative amino acid sequence, wherein said chimeric adenovirus coat protein binds a novel endogenous binding site present on a cell surface and directs entry into cells of a nucleic acid attached to said chimeric adenovirus coat protein by a protein/DNA interaction more efficiently than a corresponding wild-type adenovirus coat protein.
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39. A transfer vector selected from the group consisting of pAd NS 83-100 UTV and pAd BS 59-100 UTV.
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40. An adenoviral vector that comprises or encodes a chimeric adenovirus fiber protein comprising a nonnative amino acid sequence, wherein said chimeric adenovirus fiber protein directs entry into cells of a vector comprising said chimeric adenovirus fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than said chimeric adenovirus fiber protein, and wherein said fiber protein comprises a sequence selected from the group consisting of SEQ ID NO:
- 4 and SEQ ID NO;
5, and wherein the length of the polylysine string can vary from about 3 to about 30 residues.
- 4 and SEQ ID NO;
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47. A method of making an adenoviral vector that comprises or encodes a chimeric adenovirus fiber protein comprising a nonnative amino acid sequence, wherein said chimeric adenovirus fiber protein directs entry into cells of a vector comprising said chimeric adenovirus fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than said chimeric adenovirus fiber protein,
wherein said method comprises providing to a cell that does not comprise any E4 complementing sequences: - (a) a linear vector comprising the chimeric fiber and a wild-type E4 gene, and (b) a linear vector that is E4-.
Specification