SIMIAN SUBFAMILY E ADENOVIRUSES SAdV-39, -25.2, -26, -30, -37, AND -38 AND USES THEREOF

Abstract

A recombinant vector comprises simian adenovirus SAdV-39, -25.2, -26, -30, -37, and -38 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus SAdV-39, -25.2, -26, -30, -37, and -38 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

1 . An adenovirus having a capsid comprising a capsid protein selected from the group consisting of:
 (a) a hexon protein of SAdV-25.2 with the amino acids 1 to 933 of SEQ ID NO: 140; a hexon protein of SAdV-37 with the amino acids 1 to 942 of SEQ ID NO: 43; a hexon protein of SAdV-38 with the amino acids 1 to 930 of SEQ ID NO: 75; a hexon protein of SAdV-26 with the amino acids 1 to 937 of SEQ ID NO: 172;   (b) a penton protein of SAdV-25.2 with the amino acids 1 to 531 of SEQ ID NO: 135; a penton protein of SAdV-39 with the amino acids 1 to 532 of SEQ ID NO: 6; a penton protein of SAdV-30 with the amino acids 1 to 533 of SEQ ID NO: 103; a penton protein of SAdV-37 with the amino acids 1 to 542 of SEQ ID NO: 38; a penton protein of SAdV-38 with the amino acids 1 to 539 of SEQ ID NO: 70; a penton protein of SAdV-26 with the amino acids 1 to 546 of SEQ ID NO: 167; and   (c) a fiber protein of SAdV-25.2 with the amino acids 1 to 443 of SEQ ID NO: 151; a fiber protein of SAdV-39 with the amino acids 1 to 489 of SEQ ID NO: 22, a fiber protein of SAdV-30 with the amino acids 1 to 445 of SEQ ID NO: 118; a fiber protein of SAdV-37 with the amino acids 1 to 445 of SEQ ID NO: 54; a fiber protein of SAdV-38 with the amino acids 1 to 425 of SEQ ID NO: 85; a fiber protein of SAdV-26 with the amino acids 1 to 425 of SEQ ID NO: 183; and   said capsid encapsidating a heterologous nucleic acid comprising a gene operably linked to expression control sequences which direct transcription, translation, and/or expression thereof in a host cell.   
     
     
         2 . The adenovirus according to  claim 1 , further comprising a 5′ and a 3′ adenovirus cis-element necessary for replication and encapsidation. 
     
     
         3 . The adenovirus according to  claim 1 , wherein said adenovirus lacks all or a part of the E1 gene. 
     
     
         4 . The adenovirus according to  claim 3 , wherein said adenovirus is replication—defective. 
     
     
         5 . The adenovirus according to  claim 1 , wherein said capsid is a hybrid capsid. 
     
     
         6 . The adenovirus according to  claim 5 , wherein said hybrid capsid comprises at least one capsid protein selected from one or more adenoviruses selected from SAdV-39, SAdV-30, SAdV-37, SAdV-38, and SAdV-26. 
     
     
         7 . An adenovirus having a capsid comprising a hexon containing a fragment of a simian adenovirus hexon protein and a nucleic acid sequence heterologous to the SAdV, wherein the fragment of the SAdV hexon protein is the SAdV hexon protein of SEQ ID NO: 140, 43, 75 or 172 with an N-terminal or C-terminal truncation of about 50 amino acids in length or is selected from the group consisting of:
 amino acid residues 125 to 443 of SEQ ID NO: 140, 43, 75 or 172;   amino acid residues 138 to 441 of SEQ ID NO: 140, 43, 75 or 172;   amino acid residues 138 to 163 of SEQ ID NO: 140, 43, 75 or 172;   amino acid residues 170 to 176 of SEQ ID NO: 140, 43, 75 or 172; and   amino acid residues 404 to 430 of SEQ ID NO: 140, 43, 75 or 172.   
     
     
         8 . The adenovirus according to  claim 7 , wherein the capsid further comprises a SAdV-39, SAdV-30, SAdV-25.2, SAdV-37, SAdV-38 or SAdV-26 fiber protein. 
     
     
         9 . The adenovirus according to  claim 7 , wherein the capsid further comprises a SAdV-39, SAdV-30, SAdV-25.2, SAdV-37, SAdV-38 or SAdV-26 penton protein. 
     
     
         10 . The adenovirus according to  claim 7 , wherein said adenovirus is a pseudotyped adenovirus comprising 5′ and 3′ adenovirus cis-elements necessary for replication and encapsidation, said cis-elements comprising an adenovirus 5′ inverted terminal repeat and an adenovirus 3′ inverted terminal repeat. 
     
     
         11 . The adenovirus according to  claim 7 , wherein the adenovirus comprises a nucleic acid sequence encoding a product operatively linked to sequences which direct expression of said product in a host cell. 
     
     
         12 . The adenovirus according to  claim 7 , wherein the adenovirus comprises one or more adenovirus genes. 
     
     
         13 . The recombinant adenovirus according to  claim 7 , wherein the adenovirus is replication-defective. 
     
     
         14 . The recombinant adenovirus according to  claim 13 , wherein the adenovirus is deleted in adenovirus E1. 
     
     
         15 . A composition comprising the adenovirus according to  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         16 . A method for targeting a cell having an adenoviral receptor comprising delivering to a subject an adenovirus according to  claim 1 . 
     
     
         17 . A composition comprising the adenovirus according to  claim 1  in a pharmaceutically acceptable carrier, said adenovirus further comprising one or more simian adenovirus protein selected from the group consisting of:
 E1a, selected from the amino acid sequence of SEQ ID NO: 30, 127, 159, 62, 95 and 191; 
 E1b, small T/19K, selected from the amino acid sequence of SEQ ID NO: 24, 120, 153, 56, 89, and 185; 
 E1b, large T/55K, selected from the amino acid sequence of SEQ ID NO: 2, 99, 131, 34, 66, and 163; 
 IX, selected from the amino acid sequence of SEQ ID NO: 3, 100, 132, 35, 67, and 164; 
 52/55D, selected from the amino acid sequence of SEQ ID NO: 4, 101, 133, 36, 68, and 165; 
 IIIa, selected from the amino acid sequence of SEQ ID NO: 5, 102, 134, 37, 69 and 166; 
 VII, selected from the amino acid sequence of SEQ ID NO: 7, 104, 136, 39, 71, and 168; 
 V, selected from the amino acid sequence of SEQ ID NO: 8, 105, 137, 40, 72, and 169; 
 pX, selected from the amino acid sequence of SEQ ID NO: 9, 106, 138, 41, 73, and 170; 
 VI, selected from the amino acid sequence of SEQ ID NO: 10, 107, 139, 42, 74, and 171; 
 Endoprotease, selected from the amino acid sequence of SEQ ID NO: 12, 109, 141, 44, 76, and 173; 
 100 kD, selected from the amino acid sequence of SEQ ID NO: 13, 110, 142, 45, 77, and 174; 
 33 kD, selected from the amino acid sequence of SEQ ID NO: 32, 129, 161, 64, 97, 97, and 193; 
 22 kD, selected from the amino acid sequence of SEQ ID NO: 26, 122, 155, 58, 91, and 187; 
 VIII, selected from the amino acid sequence of SEQ ID NO: 14, 111, 143, 46, 78, and 175; 
 E3/12.5 K, selected from the amino acid sequence of SEQ ID NO: 15, 123, 144, 47, 79, and 176; 
 CR1-alpha, selected from the amino acid sequence of SEQ ID NO: 27, 112, 156, 59, 92, and 188; 
 gp19K, selected from the amino acid sequence of SEQ ID NO: 16, 124, 145, 48, 87, and 177; 
 CR1-beta, selected from the amino acid sequence of SEQ ID NO: 17, 113, 146, 49, 80, and 178; 
 CR1-gamma, selected from the amino acid sequence of SEQ ID NO: 18, 114, 147, 50, 81, and 179; 
 CR1-delta, selected from the amino acid sequence of SEQ ID NO: 19, 115, 148, 51, 82, 180; 
 RID-alpha, selected from the amino acid sequence of SEQ ID NO: 20, 116, 149, 52, 83, and 181; 
 RID-beta, selected from the amino acid sequence of SEQ ID NO: 21, 117, 150, 53, 93, and 182; and 
 E3/14.7K, selected from the amino acid sequence of SEQ ID NO: 28, 125, 158, 60, 84, and 189. 
 
     
     
         18 . A method for targeting a cell having an adenoviral receptor comprising delivering to a subject a composition according to  claim 17 .