کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6141679 | 1227268 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 (VNAR) of the shark immunoglobulin new antigen receptor (IgNAR) antibodies. VNARs possess advantages in stability, size (~ 14 kDa) and cryptic epitope recognition compared to conventional antibodies. The VNAR 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 VNAR 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 411, Issue 1, 1 March 2011, Pages 132-141
Journal: Virology - Volume 411, Issue 1, 1 March 2011, Pages 132-141
نویسندگان
Renae Walsh, Stewart Nuttall, Peter Revill, Danni Colledge, Liza Cabuang, Sally Soppe, Olan Dolezal, Kate Griffiths, Angeline Bartholomeusz, Stephen Locarnini,