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Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody.

Abstract：

:The Hepatitis B virus precore protein is processed in the endoplasmic reticulum (ER) into secreted hepatitis B e antigen (HBeAg), which acts as an immune tolerogen to establish chronic infection. Downregulation of secreted HBeAg should improve clinical outcome, as patients who effectively respond to current treatments (IFN-α) have significantly lower serum HBeAg levels. Here, we describe a novel reagent, a single variable domain (V(NAR)) of the shark immunoglobulin new antigen receptor (IgNAR) antibodies. V(NAR)s possess advantages in stability, size (~14 kDa) and cryptic epitope recognition compared to conventional antibodies. The V(NAR) domain displayed biologically useful affinity for recombinant and native HBeAg, and recognised a unique conformational epitope. To assess therapeutic potential in targeting intracellular precore protein to reduce secreted HBeAg, the V(NAR) was engineered for ER-targeted in vitro delivery to function as an intracellular antibody (intrabody). In vitro data from HBV/precore hepatocyte cell lines demonstrated effective intrabody regulation of precore/HBeAg.

journal_name

Virology

journal_title

Virology

authors

Walsh R,Nuttall S,Revill P,Colledge D,Cabuang L,Soppe S,Dolezal O,Griffiths K,Bartholomeusz A,Locarnini S

doi

10.1016/j.virol.2010.12.034

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

132-41

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(10)00791-9

journal_volume

411

pub_type

杂志文章

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