US2007259339A1PendingUtilityA1

Methods and reagents for genotyping hcv

48
Assignee: HNATYSZYN JAMESPriority: Dec 23, 2005Filed: Dec 22, 2006Published: Nov 8, 2007
Est. expiryDec 23, 2025(expired)· nominal 20-yr term from priority
C12Q 1/707C12N 2770/24211
48
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Claims

Abstract

The present invention is directed to methods and reagents for determining the genotype of a hepatitis C virus (HCV) species present in a test sample. The invention more particularly relates to mixtures of degenerate amplification and sequencing primers, and methods of using such primers, that are complementary to a plurality of HCV species, and are capable of generating nucleotide sequence information for a region of NS5B of HCV that is, for each species, indicative of the type and/or subtype, of the species present in the sample.

Claims

exact text as granted — not AI-modified
1 . A method for determining the genotype of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) determining the nucleotide sequence of at least a portion of the NS5b region of HCV indicative of the genotype of said HCV species present in the test sample, wherein the corresponding nucleotide sequence of a plurality of HCV species is indicative of a distinct genotype of that HCV species;    (b) correlating the nucleotide sequence of said portion of the NS5b region determined in (a) with the genotype of one of said plurality of HCV species.    
     
     
         2 . The method of  claim 1 , wherein the portion of the NS5b region of HCV consists essentially of the region from about nucleotide position 8344 to about 8547 of SEQ ID NO: 1.  
     
     
         3 . The method of  claim 1 , wherein the portion of the NS5b region of HCV consists essentially of the region from nucleotide position 8344 to 8547 of SEQ ID NO: 1.  
     
     
         4 . A method for determining the genotype of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) determining the nucleotide sequence of at least a portion of the NS5b region of HCV indicative of the genotype of said HCV species present in the test sample, wherein the corresponding nucleotide sequence of each of a plurality of HCV species having HCV genotypes 1, 2, 3, 4, 5, and 6 is indicative of a distinct genotype of that HCV species;    (b) correlating the nucleotide sequence of said portion of the NS5b region determined in (a) with one of said HCV genotypes 1, 2, 3, 4, 5 and 6.    
     
     
         5 . The method of  claim 4 , wherein the portion of the NS5b region of HCV consists essentially of the region from about nucleotide position 8344 to about 8547 of SEQ ID NO: 1.  
     
     
         6 . The method of  claim 4 , wherein the portion of the NS5b region of HCV consists essentially of the region from nucleotide position 8344 to 8547 of SEQ ID NO: 1.  
     
     
         7 . A method for determining the genotype and subtype of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) determining the nucleotide sequence of at least a portion of the NS5b region of HCV indicative of the genotype and subtype of said HCV species present in the test sample, wherein the corresponding nucleotide sequence of each of a plurality of HCV species having HCV genotypes 1, 2, 3, 4, 5, and 6, and each of the HCV subtypes set forth in Table 1, is indicative of a distinct genotype and subtype of that HCV species;    (b) correlating the nucleotide sequence of said portion of the NS5b region determined in (a) with one of said HCV genotypes 1, 2, 3, 4, 5 and 6 and one of said subtypes set forth in Table 1.    
     
     
         8 . The method of  claim 7 , wherein the portion of the NS5b region of HCV, consists essentially of the region from about nucleotide position 8344 to about 8547 of SEQ ID NO: 1.  
     
     
         9 . The method of  claim 7 , wherein the portion of the NS5b region of HCV consists essentially of the region from nucleotide position 8344 to 8547 of SEQ ID NO: 1.  
     
     
         10 . A method for determining the genotype of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) providing a mixture of degenerate oligonucleotide sequencing primers capable of generating nucleotide sequence of at least a portion of the NS5b region of a plurality of HCV species, wherein the corresponding nucleotide sequence of each of said plurality of HCV species is indicative of a distinct genotype of that HCV species;    (b) determining the nucleotide sequence of said portion of the NS5b region indicative of the genotype of said HCV species present in the test sample; and    (c) correlating the nucleotide sequence of said portion of the NS5b region of said HCV species determined in (b) with a genotype of one of said plurality of HCV species.    
     
     
         11 . The method of  claim 10 , wherein the mixture of degenerate oligonucleotide sequencing primers comprises degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8256 to about 8278, or its complement, and degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8611 to about 8633 of SEQ ID NO: 1, or its complement.  
     
     
         12 . The method of  claim 10 , wherein the mixture of degenerate oligonucleotide sequencing primers comprises degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8256 to 8278, or its complement, and degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8611 to 8633 of SEQ ID NO: 1, or its complement.  
     
     
         13 . The method of  claim 10 , wherein the mixture of degenerate oligonucleotide sequencing primers comprise degenerate oligonucleotide sequences defined by the following formulas, or complements thereof:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:1: 
                     
                 
                     
                   5′-TAT GAY ACC CGC TGY TTY GAY TC-3′; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID NO:2: 
                 
                     
                   5′-VGT CAT RGC ITC YGT RAA GGC TC-3′. 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         14 . A method for determining the genotype of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) providing a mixture of degenerate oligonucleotide sequencing primers capable of generating nucleotide sequence of at least a portion of the NS5b region of a plurality of HCV species, wherein the corresponding nucleotide sequence of each of said plurality of HCV species is indicative of one of HCV genotypes 1, 2, 3, 4, 5 and 6;    (b) determining the nucleotide sequence of said portion of the NS5b region indicative of the genotype of said HCV species present in the test sample; and    (c) correlating the nucleotide sequence of said portion of the NS5b region of said HCV species determined in (b) with one of HCV genotypes 1, 2, 3, 4, 5 and 6.    
     
     
         15 . The method of  claim 14 , wherein the mixture of degenerate oligonucleotide sequencing primers comprises degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8256 to about 8278, or its complement, and degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8611 to about 8633 of SEQ ID NO: 1, or its complement.  
     
     
         16 . The method of  claim 14 , wherein the mixture of degenerate oligonucleotide sequencing primers comprises degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8256 to 8278, or its complement, and degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8611 to 8633 of SEQ ID NO: 1, or its complement.  
     
     
         17 . The method of  claim 14 , wherein the mixture of degenerate oligonucleotide sequencing primers comprise degenerate oligonucleotide sequences defined by the following formulas, or complements thereof:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:1: 
                     
                 
                     
                   5′-TAT GAY ACC CGC TGY TTY GAY TC-3′; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID NO:2: 
                 
                     
                   5′-VGT CAT RGC ITC YGT RAA GGC TC-3′. 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         18 . A method for determining the genotype of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) providing a mixture of degenerate oligonucleotide sequencing primers capable of generating nucleotide sequence of at least a portion of the NS5b region of a plurality of HCV species, wherein the corresponding nucleotide sequence of each of said plurality of HCV species is indicative of one of HCV genotypes 1, 2, 3, 4, 5 and 6 and one of the subtypes;    (b) determining the nucleotide sequence of said portion of the NS5b region indicative of the genotype and subtype of said HCV species present in the test sample; and    (c) correlating the nucleotide sequence of said portion of the NS5b region of said HCV species determined in (b) with an HCV genotype and subtype.    
     
     
         19 . The method of  claim 18 , wherein the mixture of degenerate oligonucleotide sequencing primers comprises degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8256 to about 8278, or its complement, and degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8611 to about 8633 of SEQ ID NO: 1, or its complement.  
     
     
         20 . The method of  claim 18 , wherein the mixture of degenerate oligonucleotide sequencing primers comprises degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8256 to 8278, or its complement, and degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8611 to 8633 of SEQ ID NO: 1, or its complement.  
     
     
         21 . The method of  claim 18 , wherein the mixture of degenerate oligonucleotide sequencing primers comprise degenerate oligonucleotide sequences defined by the following formulas, or complements thereof:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:1: 
                     
                 
                     
                   5′-TAT GAY ACC CGC TGY TTY GAY TC-3′; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID NO:2: 
                 
                     
                   5′-VGT CAT RGC ITC YGT RAA GGC TC-3′. 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         22 . A method for amplifying a portion of the NS5b region of a hepatitis C virus (HCV) species present in a test sample, comprising: 
 (a) providing a mixture of degenerate oligonucleotide PCR primers comprising:    degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8245 to about 8269, or its complement; and    degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from about nucleotide 8616 to about 8641 of SEQ ID NO: 1, or its complement; and    (b) amplifying the nucleotide sequence of said portion of the NS5b region.    
     
     
         23 . The method of  claim 22 , wherein the mixture of degenerate oligonucleotide PCR primers comprises: 
 degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8256 to 8278, or its complement; and    degenerate nucleotide sequences complementary to the NS5b region of a plurality of HCV species from nucleotide 8611 to 8633 of SEQ ID NO: 1, or its complement.    
     
     
         24 . The method of  claim 22 , wherein the mixture of degenerate oligonucleotide PCR primers comprise degenerate oligonucleotide sequences defined by the following formulas, or complements thereof:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:6: 
                     
                 
                     
                   5′- TGG SBT TYK CNT AYG AYA CYM GNT G - 3′ 
                 
                     
                     
                 
                     
                   SEQ ID NO:5: 
                 
                     
                   5′- GAR TAY CTV GTC ATR GCI TCY GTR AA - 3′ 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         25 . The method of  claim 22 , wherein the mixture of degenerate oligonucleotide PCR primers comprise degenerate oligonucleotide sequences defined by the following formulas, or complements thereof:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:3: 
                     
                 
                     
                   5′- TGG GGT TCK CGT ATG AYA CCC GCT G - 3′ 
                 
                     
                     
                 
                     
                   SEQ ID NO:4: 
                 
                     
                   5′- TGG GGT TCK CIT ATG AYA CYM GIT G - 3′ 
                 
                     
                     
                 
                     
                   SEQ ID NO:5: 
                 
                     
                   5′- GAR TAY CTV GTC ATR GCI TCY GTR AA - 3′ 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         26 . A mixture of degenerate oligonucleotide PCR primers, wherein the mixture comprises a plurality of oligonucleotide PCR primers defined by one or more of the following formulas:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:3: 
                     
                 
                     
                   5′- TGG GGT TCK CGT ATG AYA CCC GCT G - 3′ 
                 
                     
                     
                 
                     
                   SEQ ID NO:4: 
                 
                     
                   5′- TGG GGT TCK CIT ATG AYA CYM GIT G - 3′ 
                 
                     
                     
                 
                     
                   SEQ ID NO:5: 
                 
                     
                   5′- GAR TAY CTV GTC ATR GCI TCY GTR AA - 3′ 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         27 . The mixture of degenerate oligonucleotide PCR primers of  claim 26 , wherein the mixture comprises a plurality of oligonucleotide PCR primers defined by the following formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:3: 
                     
                 
                     
                   5′- TGG GGT TCK CGT ATG AYA CCC GCT G - 3′ 
                 
                     
                     
                 
             
                
                
                
                
               
            
           
         
       
     
     
         28 . The mixture of degenerate oligonucleotide PCR primers of  claim 26 , wherein the mixture comprises a plurality of oligonucleotide PCR primers defined by the following formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:4: 
                     
                 
                     
                   5′- TGG GGT TCK CIT ATG AYA CYM GIT G - 3′ 
                 
                     
                     
                 
             
                
                
                
                
               
            
           
         
       
     
     
         29 . The mixture of degenerate oligonucleotide PCR primers of  claim 26 , wherein the mixture comprises a plurality of oligonucleotide PCR primers defined by the following formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:5: 
                     
                 
                     
                   5′- TGG GGT TCK CIT ATG AYA CYM GIT G - 3″ 
                 
                     
                     
                 
             
                
                
                
                
               
            
           
         
       
     
     
         30 . A mixture of degenerate oligonucleotide sequencing primers, wherein the mixture comprises a plurality of oligonucleotide sequencing primers defined by one or more of the following formulas:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:1: 
                     
                 
                     
                   5′- TAT GAY ACC CGC TGY TTY GAY TC - 3′; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID NO:2: 
                 
                     
                   5′- VGT CAT RGC ITC YGT RAA GGC TC - 3′. 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         31 . The mixture of degenerate oligonucleotide sequencing primers of  claim 30 , wherein the mixture comprises a plurality of oligonucleotide sequencing primers defined by the following formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:1: 
                     
                 
                     
                   5′- TAT GAY ACC CGC TGY TTY GAY TC - 3′; 
                 
                     
                   and 
                 
                     
                     
                 
             
                
                
                
                
                
               
            
           
         
       
     
     
         32 . The mixture of degenerate oligonucleotide sequencing primers of  claim 30 , wherein the mixture comprises a plurality of oligonucleotide sequencing primers defined by the following formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO:2: 
                     
                 
                     
                   5′- VGT CAT RGC ITC YGT RAA GGC TC -3′.

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