Fox Chase Cancer Center Background
HBV is the causative agent of hepatitis B. In about a third of afflicted individuals this form of hepatitis becomes a chronic condition in which liver tissue is constantly undergoing regeneration due to continuous scarring by viral replication. The damage can result in cirrhosis of the liver and the constant regeneration environment over many years can lead to the development of hepatocellular carcinoma. Currently, there is an outstanding vaccine for hepatitis B but even with a number of treatment regimens for already infected individuals, there is no definitive cure. The cost of medicines and/or transplant intervention, the morbidity and mortality associated with hepatitis B drive a search for better treatments. The present technologies can address both viral load in the liver and other liver diseases that may or may not be associated with HBV infection.
Technology Overview
Researchers at the Fox Chase Cancer Center have developed a suite of tools with promise to treat hepatitis B infection and other liver disorders. The technologies include a delivery vector that targets human hepatocytes and two methods of interfering with entry of Hepatitis B virus (HBV) particles into cells.
The method can prevent infection of hepatocytes by HBV. The current technology proposes two approaches to infection prevention: by recombinant secreted HBV proteins and by subviral particles. Both technologies are believed to prevent binding and/or internalization of HBV particles.
Further Details:
Chai N, Chang HE, Nicolas E, Han Z, Jarnik M, Taylor J. Properties of Subviral Particles of Hepatitis B Virus. J Virol. 2008 Jun 4.
Chai N, Chang HE, Nicolas E, Gudima S, Chang J, Taylor J. Assembly of hepatitis B virus envelope proteins onto a lentivirus pseudotype that infects primary human hepatocytes. J Virol. 2007 Oct;81(20):10897-904
Chai N, Gudima S, Chang J, Taylor J. Immunoadhesins containing pre-S domains of hepatitis B virus large envelope protein are secreted and inhibit virus infection. J Virol. 2007 May;81(10):4912-8
Applications
The proteins can be further developed into therapeutics to be used both as a preventive measure as well as treatment, which could halt progression of HBV infection. The delivery vector proposed by the technology involves a lentivirus pseudotyped with HBV envelope proteins. The lentivirus can thus be used in a variety of gene therapy applications in human hepatocytes including viral infection and genetic liver disorders.
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