Research Description:

Single-Chain FV Molecules Against HCV RNA Polymerase

Hepatitis C (HCV) is a progressive viral disease of the liver that affects about 28,000 every year and results in over 10,000 deaths annually. By nature, the virus has a high propensity to mutate, which explains difficulties in vaccine development and lack of response to current therapy. Nonetheless, important diagnostic and clinical implications from the extensive genetic heretogeneity of HCV has spurred the search for antiviral strategies.

The aim of this project is to develop a novel antiviral strategy against Hepatitis C virus by interfering with HCV RNA polymerase (NS5) activity. RNA polymerase (NS5) is chosen as the target because it is an essential enzyme used in Hepatitis C virus DNA replication, primarily responsible for the first step in transcribing the virusÅf genetic information to mRNA. Therefore in theory, to target and hamper this enzyme ceases virus replication and prepotency. In this project, the experimental approach to inhibit HCV RNA Polymerase (NS5) activity is by delivering a generated expression plasmid of single-chain fragment molecules (scFv) into the HCV replicon cell line. The antiviral efficacy of the scFv is then evaluated. The single-chain Fv molecule is made from clones of the low-variable (VL) and high-variable (VH) gene fragments in the HCV NS5 antibody. Thus, the hypothesis is that the scFv inside HCV cells will bind to its NS5 antigen target, interfering with NS5 activity, and subsequently inhibiting viral replication.