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HBV Platform

Overview

Chronic hepatitis B (CHB) is a severe public health burden and an unmet medical need. Current standard therapies, interferon-α and nucleot(s)ides, cannot eliminate HBV. Recently, various novel targets and approaches are being explored towards the cure of CHB.  The Biology HBV team in Research Service Division (RSD) at WuXi AppTec, led by a group of experienced scientists with in-depth knowledge in anti-HBV drug discovery, has established and been providing an open access and full-range integrated HBV platform to our clients, including biochemical and cell-based assays, ex vivo PHH systems, animal models and clinical virology assays. The WuXi HBV team is your ideal partner for discovery and development of novel anti-HBV agents.

 

Services

A broad assay platform for the discovery of agents for the treatment of chronic HBV infection. Services for assay establishment and validation, compound screening and characterization, and support of preclinical studies and clinical trials.

 

In Vitro Assays

  • (1) HBV stable cell lines : HepG2.2.15, DE19 and DES19
  •     -HBV DNA, cccDNA (qPCR, dot blot, Southern blot)
  •     -HBV antigens (ELISA, IHC, Western blot)
  •     -HBV RNAs (Northern blot, RT-qPCR)
  •     -Encapsidated RNA and DNA
  •     -Capsid content
  • (2) HBV DNA constructs with transient transfection assay
  • (3) Clinical isolates/genotype A to J (~5 strains for each genotype)
  • (4) Nucleot(s)ide and capsid inhibitor resistant mutants
  • (5) Phenotyping with shuttle vectors and mutant constructs
  •     -Fitness
  •     -Drug sensitivity
  • (6) HepG2-NTCP cell/HBV infectious system
  • (7) Reporter cell lines (hTLR, THP1-Blue ISG, TNF-induced NF-κB-luciferase, and IFN-α/β induction SEAP)
  • (8) Production of HBV from HBV stable cell lines
  • (9) Recombinant core protein expression and purification, and capsid quenching assay
  • (10) MOA studies

 

Ex Vivo Primary Human Hepatocytes (PHH)

  • Fresh isolated and cryopreserved PHH
  • In vitro HBV infection
  • In vivo HBV infection 

 

PK/PD Study and HBV Animal Model Related Immunology Assays

  • Cytokines by ELISA, Luminex and MSD
  • IFN and ISG mRNA by ELISA and RT-qPCR
  • Immune markers by IHC, IF and Western blot
  • Splenocytes, lymphocytes from organs and PBMC by FACS, ICS and ELISPOT 

 

Animal Models

  • Hydrodynamic injection (HDI) mouse model
  • AAV/HBV mouse model
  • Humanized FRG mouse model
  • WHV/woodchuck model

 

Activity of ETV in AAV/HBV Mice

 

 

Clinical Virology (CAP lab)

  • Viral load (Cobas)
  • Sequencing: Pol, core, full-length sequencing, sanger (clone and population), deep sequencing
  • Genotyping by INNO-LiPA
  • Phenotyping
  • HBV emerging markers: serum HBV RNA, HBcrAg