Viral vectors with modified transduction profiles and methods of making and using the same
AssigneeThe University of North Carolina at Chapel Hill
InventorsAravind Asokan, Nagesh Pulicherla
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Abstract
The present invention provides AAV capsid proteins, virus capsids comprising said capsid proteins and virus vectors comprising said capsid proteins, wherein the AAV capsid proteins have one or more mutations, wherein the mutation(s) result in a phenotype of decreased liver transduction and/or reduced glycan binding affinity as compared to a control. The invention also provides methods of administering the virus vectors and virus capsids of the invention to a cell or to a subject.
Claims20
A Clade F adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution in one or more of amino acids N498, S499, E500, F501, A502, W503 and P504 (according to AAV9 VP1 numbering), in any combination, wherein the substitution in the capsid protein results in a Clade F viral phenotype of decreased transduction of liver cells as compared to a Clade F control or wild-type virus.
A Clade F AAV capsid protein comprising a W503R substitution (according to AAV9 VP1 numbering), wherein the substitution in the capsid protein results in a Clade F viral phenotype of decreased transduction of liver cells as compared to a Clade F control or wild-type virus.
A Clade F AAV capsid protein comprising a N498Y substitution (according to AAVP1 numbering), wherein the substitution in the capsid protein results in a Clade F viral phenotype of decreased transduction of liver cells as compared to a Clade F control or wild-type virus.
A Clade F AAV capsid protein comprising a N4981 substitution (according to AAV9 VP1 numbering, wherein the substitution in the capsid protein results in a Clade F viral phenotype of decreased transduction of liver cells as compared to a Clade F control or wild-type virus.
A Clade F adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution in one or more of amino acids N498, S499, E500, F501, A502, W503 and P504 (according to AAV9 VP1 numbering), in any combination, wherein the substitution in the capsid protein results in a Clade F viral phenotype of reduced glycan binding affinity as compared to a Clade F control or wild-type virus.
A Clade F AAV capsid protein comprising a W503R substitution (according to AAV9 VP1 numbering), wherein the substitution in the capsid protein results in a Clade F viral phenotype of reduced glycan binding affinity as compared to a Clade F control or wild-type virus.
A Clade F AAV capsid protein comprising a N498Y substitution (according to AAV9 VP1 numbering), wherein the substitution in the capsid protein results in a Clade F viral phenotype of reduced glycan binding affinity as compared to a Clade F control or wild-type virus.
A Clade F AAV capsid protein comprising a N498I substitution (according to AAV9 VP1 numbering), wherein the substitution in the capsid protein results in a Clade F viral phenotype of reduced glycan binding affinity as compared to a Clade F control or wild-type virus.
Dependencies are inferred from the claim text.