In:
The Journal of Gene Medicine, Wiley, Vol. 10, No. 6 ( 2008-06), p. 619-627
Abstract:
Interferon‐α2 (IFNα2) is routinely used for anti‐hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half‐life, relatively low local concentration and strong side‐effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector‐delivered IFNα1 was tested for its anti‐HBV effects. Methods Adeno‐associated viral vector (AAV‐IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme‐linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real‐time polymerase chain reaction. Results AAV‐IFNα1 effectively transduced HBV‐producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro . In the HBV‐producing mice, the concentration of IFNα1 in the liver was eight‐fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten‐fold from day 1–5, and dropped to an undetectable level on day 9 in the AAV‐IFNα1 group. Concurrently, the level of viral DNA decreased over 30‐fold for several weeks. Conclusions A single dose administration of AAV‐IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo . Therefore, the use of AAV‐IFNα1 might be a potential alternative strategy for anti‐HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.
Type of Medium:
Online Resource
ISSN:
1099-498X
,
1521-2254
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
2002203-7
SSG:
12
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