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RECOMBINANT HBXAG PRODUCTION FOR ANTI-CANCER THERAPEUTIC

Award Number: R43CA105919
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/17/2004
PERIOD OF PERFORMANCE END DATE: 11/16/2004

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RECOMBINANT HBXAG PRODUCTION FOR ANTI-CANCER THERAPEUTIC - DESCRIPTION (provided by investigator): Chronic infection with hepatitis B virus (HBV) is associated with a high incidence of liver diseases, including hepatocellular carcinoma (HCC). Hepatitis B virus x antigen (HBxAg), one of the four proteins encoded by the virus, stimulates virus gene expression and replication, and is crucial for the establishment and maintenance of the chronic carrier state. Intrahepatic HBxAg expression also correlates with the intensity and progression of liver disease, suggesting it plays a central role in the pathogenesis of chronic infection. HBxAg transforms liver cells in vitro and in vivo, and results in the development of HCC in X transgenic mice, suggesting it plays a central role in hepatocarcinogenesis as well. Changes in hepatocellular phenotype may result, in part, from the ability of HBxAg to alter host gene expression. Together, this data (accumulated over the past 20 years) demonstrate that HBxAg is an important target for the development of specific inhibitors that would be effective against virus replication, chronic liver disease, and tumor development. The problems in developing such inhibitors involves the inability to stably express intracellular HBxAg at high levels (which is usually toxic) and the inability to isolate enough soluble HBxAg in native (functional) form in vitro to set up screening assays for drug discovery and to conduct crystallographic analysis for rationale drug design. Hence, this application proposes to express and isolate HBxAg from E. coli, to refold it in vitro, and then to test for HBxAg trans-activation function in cell based assays (aim 1). In addition, we propose to establish conditions for scale up production of HBxAg for crystallographic work and for establishing assays that would be useful for high throughput screening (aim 2). The long-term objective of this study is to obtain high-resolution structure of bioactive of HBxAg for small molecular drugs development to treat both viral infection and HCC.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2004 ( Subtotal = $100,000 )
2004	2004	PROTEOMTECH INC	5980 HORTON STREET	EMERYVILLE	CA	94608	ALAMEDA	USA	Cancer Cause and Prevention Research	000	1	5/17/2004	NEW	$100,000
														Subtotal = $100,000

Grand Total All Awards = $100,000

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RECOMBINANT HBXAG PRODUCTION FOR ANTI-CANCER THERAPEUTIC

Award Number: R43CA105919

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/17/2004

PERIOD OF PERFORMANCE END DATE: 11/16/2004

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