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3'NTR Technology |
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HCV 3' NTR The 3' Nontranslated Region (3'NTR) is the most conserved region of the HCV genome Kolykhalov et al., J. Virology 70:3363, 1996 ; Blight, KJ and Rice, CM., J. Virology 71:7345, 1997). It is likely to be a critical regulatory region and it has been shown to be required for replication of an infectious clone of HCV in chimpanzees Kolykhalov et al., Science 277:570, 1997. The 3' NTR is, therefore, an excellent genomic (RNA) target for an anti-HCV therapy.
HCV genome organization
Translation initiation Internal ribosome entry site Minus-strand initiation
HCV 3' NTR 98 bp terminus1a GGTGGCTCCATCTTAGCCCTAGTCACGGCTAGCTGTGAAAGGTCCGTGAGCCGCATGACTGCAGAGAGTGCTGATACTGGCCTCTCTGCAGATCATGT 1a .................................................................................................. 1a ...................................................g..................................c........... 1a ...................................................g.....................................t........ 1b ..........................................................................a....................... 1b .................................................................................................. 1b ..................................................................................c............... 1b ..................................................................................c............... 1b ................................................................g................................. 1b .................................................................................................. 1b .................................................................................................. 1b .................................................................................................. 1b .................................................................................................. 1b .................................................................................................. 1b .................................................................................................. 1b .................................................................................................. 2a .......................................................................c.ta.....t................. 2a .......................................................................c.ta.....t................. 2b .......................................................................c.ta.....t................. 3a .................................................................................................. 3b ......................................................t..................ta....................a.. 3 ......................................................t........................................a.. 4? .................................................................................................. 4a ..........................................................................a....................... 6 .................................................................................................. 7 ...........................................................................................t...... 8 ..........................................................................a....................... 9 ........................................................................../....................... Nucleotide sequence in the 3' NTR of 28 independently cloned isolates of HCV representing the genotypes shown on the left. Dots represent the same nucleotides as in the first isolate. U.S. 5,874,565 entitled (and related EP 0856051) was assigned to Washington University and licensed exclusively to Apath. Apath has already non-exclusively licensed rights to the 3' NTR for diagnostic applications. Rights to therapeutic applications are currently available for exclusive licensing to interested pharmaceutical companies. |