Receptor-binding pocket mutants of influenza a virus hemagglutinin for use in targeted gene delivery
AssigneeThe Trustees of the University of Pennsylvania
InventorsYasamin Mir-Shekari, Paul Bates
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Abstract
The invention relates to a lipid containing vector capable of fusing to a cell membrane and delivering a compounds contained therein to a cell, and methods of use thereof.
Claims30
A lipid-containing vector which fuses to a cell membrane, said vector comprising a mutant hemagglutinin, wherein said hemagglutinin comprises a mutation in the receptor binding pocket of said hemagglutinin, wherein said mutation substantially abrogates binding of said hemagglutinin to a sialic acid containing receptor, and further wherein said mutation does not affect the fusogenic capacity of said hemagglutinin.
A method of producing a lipid-containing vector, said method comprising pseudotyping an enveloped virus with a mutant influenza A virus hemagglutinin, wherein said mutant hemagglutinin comprises at least one amino acid substitution at residues threonine-115, glutamine-190, and leucine-226 in the receptor binding pocket of said hemagglutinin, and further wherein said substitution substantially abrogates binding of said hemagglutinin to a sialic acid containing receptor, and co-pseudotyping said virus with a targeting molecule.
An isolated nucleic acid encoding an influenza A virus hemagglutinin, wherein said nucleic acid comprises a mutation in the receptor binding pocket of said hemagglutinin, wherein said mutation substantially abrogates binding of said hemagglutinin to a sialic acid containing receptor, and further wherein said mutation does not affect the fusogenic capacity of said hemagglutinin.
An isolated influenza A virus hemagglutinin wherein said hemagglutinin comprises a mutation which substantially abrogates binding of said hemagglutinin to a sialic acid containing receptor and further wherein said mutation does not affect the fusogenic capability of said hemagglutinin.
A pseudotyped murine leukemia virus (MLV) comprising a mutant influenza A hemagglutinin, wherein said mutant hemagglutinin comprises a first mutation comprising a change from threonine to serine at amino acid 155, and further wherein said mutant hemagglutinin comprises a second mutation comprising a change from leucine to valine at amino acid 226, wherein said pseudotyped MLV expresses said mutant hemagglutinin and wherein said mutant hemagglutinin is in the envelope of said pseudotyped MLV.
A composition comprising a co-pseudotyped enveloped virus expressing a mutant hemagglutinin and a targeting molecule wherein said co-pseudotyped virus binds to a target cell expressing a receptor for said targeting molecule and further wherein said mutant hemagglutinin causes said virus to fuse with said target cell.
A method of targeting delivery of a component to a desired cell, said method comprising inserting a mutant hemagglutinin and a targeting molecule on the surface of a vector, wherein said targeting molecule mediates binding of said vector to a targeting molecule-specific receptor on said cell, and further wherein said mutant hemagglutinin mediates membrane fusion of said vector with the membrane of said cell, thereby delivering said component to said cell.
Dependencies are inferred from the claim text.