Oncolytic non-human adenoviruses and uses thereof
View Patent ↗Novel nucleic acid sequences, vectors and adenoviral genomes are provided herein. Corresponding novel adenoviruses and genotypes and compositions are also provided. The novel nucleic acid sequences, vectors, genomes, adenoviruses, genotypes and compositions are useful in therapy. The novel nucleic acid sequences, vectors, genomes, adenoviruses, genotypes and compositions are particularly useful in treating or preventing cancer.
1 . An isolated non-human primate adenovirus having a capsid comprising a penton base polypeptide, wherein the penton base polypeptide comprises:
(i) an amino acid sequence having at least 95% identity to SEQ ID NO: 26, or
(ii) the amino acid sequence of SEQ ID NO: 26;
wherein the adenovirus is conditionally replicative.
2 . An isolated non-human primate adenovirus genome encoding the adenovirus of claim 1 .
3 . A pharmaceutical composition comprising the adenovirus of claim 1 , or
the genome of claim 2 ; and
a pharmaceutically acceptable excipient, adjuvant, diluent and/or carrier.
4 . A method for targeting a cell having an adenoviral receptor in a subject, the method comprising administering the composition according to claim 3 to the subject.
5 . The adenovirus according to claim 1 , wherein the capsid comprises a hexon polypeptide comprising the amino acid sequence of SEQ ID NO: 57; and a fiber polypeptide comprising the amino acid sequence of SEQ ID NO: 56.
6 . The adenovirus according to claim 1 , wherein the capsid comprises a hexon polypeptide comprising the amino acid sequence of SEQ ID NO: 93; and a fiber polypeptide comprising the amino acid sequence of SEQ ID NO: 92.
7 . The adenovirus according to claim 1 , wherein said adenovirus lacks:
(a) all or a part of an E1 gene; and/or
(b) all or part of an E1A gene.
8 . The adenovirus according to claim 7 , wherein the E1A gene has a Δ24 deletion.
9 . The adenovirus according to claim 1 , wherein the adenovirus further comprises left-hand and right-hand side adenovirus cis-elements necessary for replication and encapsidation.
10 . The adenovirus according to claim 9 , wherein the cis-elements necessary for replication and encapsidation comprise an adenovirus left-hand side inverted terminal repeat and an adenovirus right-hand side inverted terminal repeat, and encapsidation signals.
11 . The adenovirus according to claim 1 , wherein said adenovirus comprises a hexon polypeptide comprising the amino acid sequence of SEQ ID NO: 57 or SEQ ID NO: 93.
12 . The adenovirus according to claim 1 , wherein said adenovirus comprises a fiber polypeptide, wherein said fiber polypeptide comprises:
(i) the amino acid sequence of SEQ ID NO: 56; or
(ii) an amino acid sequence having at least 95% identity to amino acid residues 127 to 320 of SEQ ID NO: 92, amino acid residues 74 to 126 of SEQ ID NO: 92, or amino acid residues 1 to 73 of SEQ ID NO: 92.
13 . The adenovirus according to claim 1 , wherein said adenovirus comprises a fiber polypeptide, wherein said fiber polypeptide comprises:
(i) the amino acid sequence of SEQ ID NO: 56; or
(ii) the amino acid sequence according to amino acid residues 127 to 320 of SEQ ID NO: 92, amino acid residues 74 to 126 of SEQ ID NO: 92, or amino acid residues 1 to 73 of SEQ ID NO: 92.
14 . The adenovirus according to claim 1 , wherein said adenovirus comprises a fiber polypeptide comprising the amino acid sequence of SEQ ID NO: 56 or 92.