An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

Jin, Young‐Hee; Kwon, Myung-Hee; Kim, Kyongmin; Shin, Hong-Jae; Shin, Jeon-Soo; Cho, Hyeseong; Park, Sun

doi:10.1007/s00262-005-0037-2

Cited by 4 publications

(6 citation statements)

References 30 publications

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“…The interaction of H7scFv with HBx inside cells and the inhibitory effect of H7scfv on HBx-induced gene activation was previously demonstrated 12. Interestingly, intracellular S2E1scFv expression also suppressed transactivation of the reporter gene in HBV-replicating HepG2-WT10 cells.…”

Section: Discussionmentioning

confidence: 63%

“…The present study was triggered by our previous work showing that intracellular H7scFv-expression suppresses HBx-mediated tumorigenicity 12. In this study, H7scFv expression inside HepG2-WT10 cells did not affect HBV replication even though it reduced gene transactivation in this cell line compared with cells transfected with control vector.…”

Section: Discussionmentioning

confidence: 69%

“…As a control, S2E1scFv specific to the small surface glycoprotein (HBsAg) of HBV was used. S2E1scFv in the cytoplasm neither interacts with HBx nor interferes with HBx function in fibroblasts expressing HBx 12. It was reported by others that an antibody fragment specific to HBsAg interfered with HBsAg secretion when it was expressed in the ER, but not in the cytoplasm, of Huh-7 cells 18.…”

Section: Resultsmentioning

confidence: 91%

“…Previously, we demonstrated that cytoplasmic expression of H7scFv, an antibody fragment specific for HBX, suppresses HBx-induced tumorigenicity and transactivation 12. Thus, to block HBx function in cells in which HBV replication occurs, H7scFv was expressed in the cytoplasm of HepG2-WT10 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The eukaryotic expression vectors for H7scFv, with specificity to HBx, and for S2E1scFv, with specificity to surface protein of HBV, were described previously 12. Briefly, variable gene segments of the immunoglobulin heavy and light chain of H7 and S2E1 respectively were linked by a (GGGGS) 3 flexible peptide linker.…”

Section: Methodsmentioning

confidence: 99%

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Intracellular Antibody Fragment Against Hepatitis B Virus X Protein Does Not Inhibit Viral Replication

et al. 2006

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Replication of the hepatitis B virus is suppressed by deficiency of the X protein. Although several molecules that block cellular targets of X protein reduce the production of hepatitis B virus progeny, the effect of a specific inhibitor of X protein on viral replication has not been investigated. To block X protein specifically, we adopted an intracellular expression approach using H7 single chain variable fragment (H7scFv), an antibody fragment against X protein. We previously demonstrated that cytoplasmic expression of H7scFv inhibits X protein-induced tumorigenicity and transactivation. In this study, intracellular H7scFv expression inhibits reporter gene transactivation but not viral replication determined by endogenous hepatitis B virus polymerase activity assay and real-time PCR. Our findings imply that intracellular expression of antibody fragment against X protein may not be an alternative therapeutic modality for inhibition of hepatitis B virus replication.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Intracellular Antibody Fragment Against Hepatitis B Virus X Protein Does Not Inhibit Viral Replication

et al. 2006

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Intracellular Antibodies (Intrabodies) and Their Therapeutic Potential

Zhu

Marasco

2008

Handbook of Experimental Pharmacology

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Combining exquisite specificity and high antigen-binding affinity, intrabodies have been used as a biotechnological tool to interrupt, modulate, or define the functions of a wide range of target antigens at the posttranslational level. An intrabody is an antibody that has been designed to be expressed intracellularly and can be directed to a specific target antigen present in various subcellular locations including the cytosol, nucleus, endoplasmic reticulum (ER), mitochondria, peroxisomes, plasma membrane and trans-Golgi network (TGN) through in frame fusion with intracellular trafficking/localization peptide sequences. Although intrabodies can be expressed in different forms, the most commonly used format is a singlechain antibody (scFv Ab) created by joining the antigen-binding variable domains of heavy and light chain with an interchain linker (ICL), most often the 15 amino acid linker (GGGGS)(3) between the variable heavy (VH) and variable light (VL) chains. Intrabodies have been used in research of cancer, HIV, autoimmune disease, neurodegenerative disease, and transplantation. Clinical application of intrabodies has mainly been hindered by the availability of robust gene delivery system(s) including target cell directed gene delivery. This review will discuss several methods of intrabody selection, different strategies of cellular targeting, and recent successful examples of intrabody applications. Taking advantage of the high specificity and affinity of an antibody for its antigen, and of the virtually unlimited diversity of antigen-binding variable domains available for molecular targeting, intrabody techniques are emerging as promising tools to generate phenotypic knockouts, to manipulate biological processes, and to obtain a more thorough understanding of functional genomics.

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Gene therapy for viral hepatitis

González‐Aseguinolaza¹,

Crettaz²,

Ochoa³

et al. 2006

Expert Opinion on Biological Therapy

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Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models.

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An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

Cited by 4 publications

References 30 publications

Intracellular Antibody Fragment Against Hepatitis B Virus X Protein Does Not Inhibit Viral Replication

Intracellular Antibody Fragment Against Hepatitis B Virus X Protein Does Not Inhibit Viral Replication

Intracellular Antibodies (Intrabodies) and Their Therapeutic Potential

Gene therapy for viral hepatitis

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