Journal
CONNECTIVE TISSUE RESEARCH
Volume 55, Issue 2, Pages 115-122Publisher
INFORMA HEALTHCARE
DOI: 10.3109/03008207.2013.862528
Keywords
Connective tissue; fibrosis; scFv; tendon
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Funding
- NIH [AR061118, AR048544]
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This study focuses on the single-chain fragment variable (scFv) variant of the original IgA-type antibody, recognizing the alpha 2 C-terminal telopeptide (alpha 2Ct) of human collagen I, designed to inhibit post-traumatic localized fibrosis via blocking the formation of collagen-rich deposits. We have demonstrated that the scFv construct expressed in yeast cells was able to fold into an immunoglobulin-like conformation, but it was prone to forming soluble aggregates. Functional assays, however, indicate that the scFv construct specifically binds to the alpha 2Ct epitope and inhibits collagen fibril formation both in vitro and in a cell culture model representing tissues that undergo post-traumatic fibrosis. Thus, the presented study demonstrates the potential of the scFv variant to serve as an inhibitor of the excessive formation of collagen-rich fibrotic deposits, and it reveals certain limitations associated with the current stage of development of this antibody construct.
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