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    Expression, Characterization, and Evaluation of a RANK-binding Single Chain Fraction Variable: An Osteoclast Targeting Drug Delivery Strategy

    Access Status
    Fulltext not available
    Authors
    Newa, M.
    Lam, M.
    Bhandari, K.
    Xu, B.
    Doschak, Michael
    Date
    2014
    Type
    Journal Article
    
    Metadata
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    Citation
    Newa, Madhuri and Lam, Michael and Bhandari, Krishna and Xu, Biwen and Doschak, Michael R. 2014. Expression, Characterization, and Evaluation of a RANK-binding Single Chain Fraction Variable: An Osteoclast Targeting Drug Delivery Strategy. Molecular Pharmaceutics. 11 (1): pp. 81-89.
    Source Title
    Molecular Pharmaceutics
    DOI
    10.1021/mp400188r
    ISSN
    1543-8384
    URI
    http://hdl.handle.net/20.500.11937/42612
    Collection
    • Curtin Research Publications
    Abstract

    A single chain Fraction variable (scFv) employs antibody-like target recognition specificity. Osteoclasts, responsible for bone resorption, express Receptor Activator of Nuclear factor Kappa B (RANK) receptors. This study aimed to express, characterize, and evaluate scFv against RANK receptors that may serve as a platform to target osteoclasts. Using phage display technology, scFv against RANK receptor was expressed and characterized by DNA sequencing, sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption–ionization time-of-flight (MALDI TOF), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunocytochemistry. The potential for cytotoxicity was evaluated using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, and its cross reactivity was evaluated using ELISA. Osteoclast-like cells were generated from RAW 264.7 cells, and the osteoclast targeting ability of scFv was evaluated using immunocytochemistry. ScFv’s antiresorptive efficacy was studied using a tartrate-resistant acid phosphatase (TRAP) assay and resorption assay. Anti-RANK scFv was successfully expressed and characterized. No cross reactivity with other tumor necrosis factor receptor (TNFR) members and no cytotoxic effect on a non-RANK bearing cell line were observed. It showed specificity toward a RANK receptor and an inhibitory effect on osteoclast activity. With the increase in development trends for biologics as therapeutics and growing knowledge on the importance of osteoclast targeted therapy, this study may provide a drug delivery strategy to target osteoclasts, thereby leading to a promising therapy for resorptive bone diseases.

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