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Aberrant cyclin D gene amplification and abnormal protein expression have been linked to hepatocellular carcinoma (HCC) tumorigenesis. Intrabodies, effective anticancer therapies that specifically inhibit target protein function within all intracellular compartments, may block cyclin D1 function. Here, a single\u2010chain variable fragment (scFv) antibody against cyclin D1 (AD\u03ba) selected from a human semi\u2010synthetic phage display scFv library is expressed in <jats:italic>Escherichia coli<\/jats:italic> as soluble AD\u03ba. Purified AD\u03ba specifically binds to recombinant and endogenous cyclin D1 with high affinity. To enable blocking of intracellular cyclin D1 activity, an endoplasmic reticulum (ER) retention signal sequence is added to the AD\u03ba sequence to encode anti\u2010cyclin D1 intrabody ER\u2010AD\u03ba. Transfection of HepG2 cells with expression vector encoding ER\u2010AD\u03ba elicited intracellular ER\u2010AD\u03ba expression leading to cyclin D1 binding, significant G1 phase arrest, and apoptosis that are mechanistically tied to decreased intracellular phosphorylated retinoblastoma protein (Rb) levels. Meanwhile, ER\u2010AD\u03ba dramatically inhibited subcutaneous human HCC xenografts growth in nude mice in vivo after injection of tumors with expression vector encoding ER\u2010AD\u03ba. These results demonstrate the potential of intrabody\u2010based cyclin D1 targeting therapy as a promising treatment for HCC.<\/jats:p>","DOI":"10.1002\/biot.201900430","type":"journal-article","created":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T08:35:06Z","timestamp":1584174906000},"source":"Crossref","is-referenced-by-count":9,"title":["A Cyclin D1\u2010Specific Single\u2010Chain Variable Fragment Antibody that Inhibits HepG2 Cell Growth and Proliferation"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-9361","authenticated-orcid":false,"given":"Yan","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Cancer Research Institute Binzhou Medical University Hospital  Binzhou 256600 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