Aav4 vector and uses thereof
OwnerJohn A. Chiorini, Robert M. Kotin +1inventors
InventorsJOHN A. CHIORINI, ROBERT M. KOTIN, BRIAN SAFER
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Abstract
The present invention provides an adeno-associated virus 4 (AAV4) virus and vectors and particles derived therefrom. In addition, the present invention provides methods of delivering a nucleic acid to a cell using the AAV4 vectors and particles.
Claims71
A nucleic acid vector comprising a pair of adeno-associated virus 4 (AAV4) inverted terminal repeats and a promoter between the inverted terminal repeats.
A nucleic acid vector comprising a pair of adeno-associated virus 4 (AAV4) inverted terminal repeats and a promoter between the inverted terminal repeats, wherein the AAV4 inverted terminal repeats comprise the nucleotide sequence set forth in SEQ ID NO:6.
A nucleic acid vector comprising a pair of adeno-associated virus 4 (AAV4) inverted terminal repeats and a promoter between the inverted terminal repeats, wherein the AAV4 inverted terminal repeats comprise the nucleotide sequence set forth in SEQ ID NO:20.
An AAV4 particle, comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4.
An isolated nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO:1.
An isolated nucleic acid consisting essentially of the nucleotide sequence set forth in SEQ ID NO:1.
An isolated nucleic acid encoding an adeno-associated virus 4 Rep protein.
An isolated AAV4 Rep protein having the amino acid sequence set forth in SEQ ID NO:2, or a unique fragment thereof.
An isolated AAV4 Rep protein having the amino acid sequence set forth in SEQ ID NO:8, or a unique fragment thereof.
An isolated AAV4 Rep protein having the amino acid sequence set forth in SEQ ID NO:9, or a unique fragment thereof.
An isolated AAV4 Rep protein having the amino acid sequence set forth in SEQ ID NO:10, or a unique fragment thereof.
An isolated AAV4 Rep protein having the amino acid sequence set forth in SEQ ID NO:11, or a unique fragment thereof.
An isolated AAV4 capsid protein having the amino acid sequence set forth in SEQ ID NO:4.
An isolated AAV4 capsid protein having the amino acid sequence set forth in SEQ ID NO:16.
An isolated AAV4 capsid protein having, the amino acid sequence set forth in SEQ ID NO:18.
An isolated nucleic acid encoding the adeno-associated virus 4 capsid protein of SEQ ID NO:16.
An isolated nucleic acid encoding the adeno-associated virus 4 capsid protein of SEQ ID NO:4.
An isolated nucleic acid that selectively hybridizes with the nucleic acid of SEQ ID NO:4.
An isolated nucleic acid comprising the AAV4 p5 promoter comprising nucleotides 130-291 of SEQ ID NO:1.
A method of screening a cell for infectivity by AAV4 comprising contacting the cell with an AAV4 particle comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4 and detecting the presence of the AAV4 particle in the cells.
A method of screening a cell for infectivity by AAV4 comprising contacting the cell with an AAV4 vector comprising an AAV4 particle comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4 and comprising a known nucleic acid, wherein the presence of the AAV4 vector is detected in the cells by detecting the presence of the known nucleic acid.
A method of determining the suitability of an AAV4 vector for administration to a subject comprising administering to an antibody-containing sample from the subject an antigenic protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11 and residues 438-601of SEQ ID NO:2 and detecting an antibody-antigen reaction in the sample, the presence of a reaction indicating the AAV4 vector to be unsuitable for use in the subject.
A method of determining the presence in a subject of an AAV4-specific antibody comprising administering to an antibody-containing sample from the subject an antigenic protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11 and residues 438-601 SEQ ID NO:4 and detecting an antibody-antigen reaction in the sample, the presence of a reaction-indicating the presence of an AAV4-specific antibody in the subject.
A method of delivering a nucleic acid to a cell comprising administering to the cell an AAV4 particle, comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4, containing a vector comprising the nucleic acid inserted between a pair of AAV inverted terminal repeats, thereby delivering the nucleic acid to the cell.
The method of claim 52, wherein the AAV inverted terminal repeats are AAV4 inverted terminal repeats.
A method of delivering a nucleic acid to a subject comprising administering to a cell from the subject an AAV4 particle, comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4, comprising the nucleic acid inserted between a pair of AAV inverted terminal repeats, and returning the cell to the subject, thereby delivering the nucleic acid to the subject.
A method of delivering a nucleic acid to a cell in a subject comprising administering to the subject an AAV4 particle, comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4, comprising the nucleic acid inserted between a pair of AAV inverted terminal repeats, thereby delivering the nucleic acid to a cell in the subject.
A method of delivering a nucleic acid to a cell in a subject having antibodies to AAV2 comprising administering to the subject an AAV4 particle, comprising a capsid protein comprising an amino acid sequence defined by amino acids 438-601 shown in SEQ ID NO:4, comprising the nucleic acid, thereby delivering the nucleic acid to a cell in the subject.
The particle of claim 61, wherein the particle is an AAV4 particle, comprising a capsid protein comprising an amino acid sequence defined by amino acids 43 8-601 shown in SEQ ID NO:4.
An isolated nucleic acid encoding, the adeno-associated virus 4 capsid protein of SEQ ID NO:18.
An AAV4 particle, comprising a capsid protein consisting essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16 and SEQ ID NO:18, containing a vector comprising a pair of AAV2 inverted terminal repeats.
A method of delivering a nucleic acid to a cell comprising administering to the cell an AAV4 particle, comprising a capsid protein consisting essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16 and SEQ ID NO:18, containing a vector comprising the nucleic acid inserted between a pair of AAV-inverted terminal repeats, thereby delivering the nucleic acid to the cell.
A method of delivering a nucleic acid to a subject comprising administering to a cell from the subject an AAV4 particle, comprising a capsid protein consisting essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16 and SEQ ID NO:18, comprising the nucleic acid inserted between a pair of AAV inverted terminal repeats, and returning the cell to the subject, thereby delivering the nucleic acid to the subject.
A method of delivering a nucleic acid to a cell in a subject comprising administering to the subject an AAV4 particle, comprising a capsid protein consisting essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16 and SEQ ID NO:18, comprising the nucleic acid inserted between a pair of AAV inverted terminal repeats, thereby delivering the nucleic acid to a cell in the subject.
A method of delivering a nucleic acid to a cell in a subject having antibodies to AAV2 comprising administering to the subject an AAV4 particle, comprising a capsid protein consisting essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:16 and SEQ ID NO:18, comprising the nucleic acid, thereby delivering the nucleic acid to a cell in the subject.
An AAV4 vector, comprising a nucleic acid selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21 and SEQ ID NO:22.
An isolated adeno-associated virus 4 Rep protein.
Dependencies are inferred from the claim text.