Seneca valley virus based compositions and methods for treating disease

Abstract

The present invention relates to a novel RNA picornavirus that is called Seneca Valley virus (“SVV”). The invention provides isolated SVV nucleic acids and proteins encoded by these nucleic acids. Further, the invention provides antibodies that are raised against the SVV proteins. Because SVV has the ability to selectively kill some types of tumors, the invention provides methods of using SVV and SVV polypeptides to treat cancer. Because SVV specifically targets certain tumors, the invention provides methods of using SVV nucleic acids and proteins to detect cancer. Additionally, due to the information provided by the tumor-specific mechanisms of SVV, the invention provides methods of making new oncolytic virus derivatives and of altering viruses to have tumor-specific tropisms.

What is claimed: 
     
         1 . An isolated nucleic acid comprising a nucleic acid sequence having at least 75% sequence identity to: (i) SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, or 168, or (ii) a contiguous portion of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, or 168, that is at least 20 nucleotides in length. 
     
     
         2 . The isolated nucleic acid of  claim 1 , wherein the nucleic acid is RNA or DNA. 
     
     
         3 . An isolated polypeptide comprising an amino acid sequence having at least 75% sequence identity to: (i) SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, or 169, or (ii) a contiguous portion of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, or 169 that is at least 10 amino acids in length. 
     
     
         4 . An isolated Seneca Valley virus or derivative thereof, comprising identifying characteristics of ATCC Patent Deposit number PTA-5343. 
     
     
         5 . An isolated Seneca Valley virus or derivative or relative thereof, having a genome comprising a sequence that is at least 95%, 90%, 85%, 80%, 75%, 70%, or 65% identical to SEQ ID NO:1 or SEQ ID NO:168. 
     
     
         6 . The virus of  claim 5  comprising the following characteristics: replication competence in tumor cells, tumor-cell tropism, and lack of cytolysis in normal cells. 
     
     
         7 . The virus of  claim 6 , wherein said virus is replication competent in tumor cell types having neuroendocrine properties. 
     
     
         8 . A pharmaceutical composition comprising an effective amount of the virus of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         9 . An isolated antibody that specifically binds to the epitope of the isolated virus of  claim 5 . 
     
     
         10 . A method for treating cancer comprising administering an effective amount of a virus or derivative thereof, so as to treat the cancer, wherein the virus has a genome that comprises a sequence that is at least 75% identical to a contiguous sequence of SEQ ID NO:1 or SEQ ID NO:168 that is at least 100 nucleotides in length. 
     
     
         11 . The method of  claim 10 , wherein the virus is a picornavirus. 
     
     
         12 . The method of  claim 11 , wherein the picornavirus is a  cardiovirus.    
     
     
         13 . The method of  claim 12 , wherein the  cardiovirus  is selected from the group consisting of: vilyuisk human encephalomyelitis virus, Theiler's murine encephalomyelitis virus, and  encephalomyocarditis  virus. 
     
     
         14 . The method of  claim 11 , wherein the picornavirus is a member of a genus to which Seneca Valley virus belongs. 
     
     
         15 . The method of  claim 11 , wherein the picornavirus is Seneca Valley virus. 
     
     
         16 . The method of  claim 15 , wherein the Seneca Valley virus has an ATCC deposit number PTA-5343. 
     
     
         17 . The method of  claim 11 , wherein the picornavirus is a Seneca Valley virus-like picornavirus. 
     
     
         18 . The method of  claim 17 , wherein the Seneca Valley virus-like picornavirus is selected from the group of isolates consisting of: MN 88-36695, NC 88-23626, IA 89-47552, NJ 90-10324, IL 92-48963, CA 131395, LA 1278, IL 66289, IL 94-9356, MN/GA 99-29256, MN 99197, and SC 363649. 
     
     
         19 . A method of killing an abnormally proliferative cell comprising contacting the cell with the virus of  claim 5 . 
     
     
         20 . A method for making an oncolytic virus, the method comprising:
 (a) comparing a Seneca Valley virus genomic sequence with a test virus genomic sequence;   (b) identifying at least a first amino acid difference between a polypeptide encoded by the Seneca Valley virus genomic sequence and a polypeptide encoded by the test virus genomic sequence;   (c) mutating the test virus genomic sequence such that the polypeptide encoded by the test virus genomic sequence has at least one less amino acid difference to the polypeptide encoded by the Seneca Valley virus genomic sequence;   (d) transfecting the mutated test virus genomic sequence into a tumor cell; and   (e) determining whether the tumor cell is lytically infected by the mutated test virus genomic sequence.   
     
     
         21 . The method of  claim 20 , wherein the Seneca Valley virus genome comprises a sequence that is at least 95% identical to SEQ ID NO:1 or SEQ ID NO:168. 
     
     
         22 . The method of  claim 20 , wherein the test virus is a picornavirus. 
     
     
         23 . The method of  claim 22 , wherein the test virus is a Seneca Valley virus-like picornavirus. 
     
     
         24 . The method of  claim 20 , wherein the amino acid differences are between a Seneca Valley virus capsid protein and a test virus capsid protein. 
     
     
         25 . The method of  claim 20 , wherein mutating the test virus genomic sequence comprises mutating a cDNA having the test virus genomic sequence. 
     
     
         26 . The method of  claim 20 , wherein transfecting the mutated test virus genomic sequence comprises transfecting RNA, wherein the RNA is generated from the cDNA having the mutated test virus genomic sequence.