USA flag logo/image

An Official Website of the United States Government

Recombinant HBxAg Production For Anti-cancer Therapeutic

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
70615
Program Year/Program:
2004 / SBIR
Agency Tracking Number:
CA105919
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
PROTEOMTECH, INC.
PROTEOMTECH, INC. 5980 HORTON ST, STE 405 EMERYVILLE, CA 94608
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2004
Title: Recombinant HBxAg Production For Anti-cancer Therapeutic
Agency: HHS
Contract: 1R43CA105919-01
Award Amount: $100,000.00
 

Abstract:

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.

Principal Investigator:

Xinli Lin
5105979134
MEDYNSKI@PROTEOMTECH-INC.COM

Business Contact:

Charles Gao
5105979133
GAO@PROTEOMTECH-INC.COM
Small Business Information at Submission:

PROTEOMTECH, INC.
PROTEOMTECH, INC. 5980 HORTON ST, STE 405 EMERYVILLE, CA 94608

EIN/Tax ID: 943397356
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No