Novel sequences encoding hepatitis c virus glycoproteins

C - Chemistry – Metallurgy – 07 – H

Patent

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Details

C07H 21/04 (2006.01) C12N 7/00 (2006.01) C12N 7/01 (2006.01) C12Q 1/70 (2006.01)

Patent

CA 2544253

The present invention concerns a modified nucleic acid molecule comprising a nucleotide sequence coding for a full length hepatitis C virus (HCV) glycoprotein selected from the group consisting of E1 glycoprotein and E1/E2 glycoprotein heterodimer, this molecule having at least one nucleotide alteration, wherein, due to this alteration, at least one RNA splice site selected from the group consisting of RNA splice acceptor and RNA splice donor sites is eliminated from the coding sequence. The invention is also directed to methods for expressing on the surface of a cell and a pseudovirion an HCV glycoprotein, wherein the majority of the glycoprotein is full length. The invention further provides a cell and a pseudovirion expressing such glycoprotein. The invention still further provides a method for determining whether an agent inhibits HCV fusion with and entry into a target cell. The invention also provides an agent that inhibits HCV fusion with and entry into a target cell. The invention further provides methods for treating a subject afflicted with an HCV-associated disorder, for preventing an HCV infection in a subject, and for inhibiting in a subject the onset of an HCV-associated disorder.

L'invention concerne une molécule d'acide nucléique modifiée contenant une séquence nucléotidique qui code une glycoprotéine du virus de l'hépatite C (VHC) pleine longueur, choisie dans le groupe glycoprotéine E1 et hétérodimère de glycoprotéine E1/E2, cette molécule présentant au moins une modification nucléotidique et, en raison de cette altération, au moins un site d'épissage d'ARN choisi dans le groupe sites d'accepteurs d'épissage d'ARN et de donneurs d'épissage ARN, est éliminé de la séquence de codage. Cette invention porte aussi sur des procédés d'expression d'une glycoprotéine VHC à la surface d'une cellule et d'un pseudovirion, les glycoprotéines étant majoritairement pleine longueur. L'invention se rapporte également à un procédé permettant de déterminer si un agent inhibe la fusion VHC au moyen d'une entrée dans une cellule cible. Elle a encore trait à des procédés de traitement d'un sujet atteint d'un trouble associé au VHC, afin d'empêcher une infection due au VHC chez un sujet, et d'inhibition, chez un sujet, de l'apparition d'un trouble associé au VHC.

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