Targeting adenovirus with use of constrained peptide motifs
First Claim
1. A chimeric adenovirus fiber protein comprising a nonnative amino acid sequence that is constrained by a non-preexisting loop.
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Abstract
The present invention provides a chimeric adenovirus fiber protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence in a conformationally-restrained manner. Such a chimeric adenovirus fiber protein according to the invention is able to direct entry into cells of a vector comprising the chimeric 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 the chimeric adenovirus fiber protein. The nonnative amino acid sequences encodes a peptide motif that comprises an epitope for an antibody, or a ligand for a cell surface receptor, that can be employed in cell targeting. The present invention also pertains to vectors comprising such a chimeric adenovirus fiber protein, and to methods of using such vectors.
226 Citations
24 Claims
- 1. A chimeric adenovirus fiber protein comprising a nonnative amino acid sequence that is constrained by a non-preexisting loop.
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11. The chimeric adenovirus fiber protein comprising a nonnative amino acid sequence, wherein said nonnative amino acid sequence is constrained in a loop comprising a set of amino acid residues selected from the group consisting of residues 403-418, 441-453, 487-514, 522-528, 537-549, and 558-572.
- 12. A chimeric adenovirus fiber protein comprising a nonnative amino acid sequence, wherein said nonnative amino acid sequence is constrained by being inserted into or in place of a loop selected from the group consisting of the AB, CD, DG, GH, HI, and IJ loops of said chimeric adenovirus fiber protein.
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23. A method of increasing the affinity of a peptide for a cell surface binding site which comprises:
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(a) obtaining a wild-type adenovirus fiber protein, and (b) inserting into or in place of a protein sequence in a loop of said knob of said wild-type adenovirus fiber protein a nonnative amino acid sequence so as to result in a chimeric adenovirus fiber protein.
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24. A method of increasing the affinity of a RGD sequence for a cell surface binding site which comprises:
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(a) obtaining a wild-type adenovirus fiber protein, and (b) inserting a RGD sequence into or in place of a protein sequence of said wild-type adenovirus fiber protein such that it is flanked by one or more cysteine pairs and is capable of forming a loop due to interaction between said cysteines.
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Specification