Patent ID: 7049428
Filing Date: 2006-05-23
Classification: C07K,C12N

Abstract:
1. A polynucleotide comprising a non-naturally occurring HCV subtype 1b sequence that is capable of productive replication in a host cell, or is capable of being transcribed into a non-naturally occurring HCV sequence that is capable of productive replication in a host cell, wherein the HCV sequence comprises, from 5′ to 3′ on the positive-sense nucleic acid, a functional 5′ non-translated region (5′ NTR); one or more protein coding regions, including at least one polyprotein coding region that is capable of replicating HCV RNA; and a functional HCV 3′ non-translated region (3′ NTR), wherein said polynucleotide further comprises an adaptive mutation in the NS5A coding region such that the adaptive mutation results in a change in the NS5A amino acid sequence selected from the group consisting of Ser (1179) to lle, Arg (1164) to Gly, Ala(1174) to Ser, Ser(1172) to Cys, and Ser(1172) to Pro of SEQ ID NO:3 that confers improved cell culture characteristics to said polynucleotide.