title: Intravenously Administered Recombinant Human Type VII Collagen Derived from Chinese Hamster Ovary Cells Reverses the Disease Phenotype in Recessive Dystrophic Epidermolysis Bullosa Mice.
abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disorder characterized by skin fragility, blistering, and multiple skin wounds with no currently approved or consistently effective treatment. It is due to mutations in the gene encoding type VII collagen (C7). Using recombinant human C7 (rhC7) purified from human dermal fibroblasts (FB-rhC7), we showed previously that intravenously injected rhC7 distributed to engrafted RDEB skin, incorporated into its dermal-epidermal junction (DEJ), and reversed the RDEB disease phenotype. Human dermal fibroblasts, however, are not used for commercial production of therapeutic proteins. Therefore, we generated rhC7 from Chinese hamster ovary (CHO) cells. The CHO-derived recombinant type VII collagen (CHO-rhC7), similar to FB-rhC7, was secreted as a correctly folded, disulfide-bonded, helical trimer resistant to protease degradation. CHO-rhC7 bound to fibronectin and promoted human keratinocyte migration in vitro. A single dose of CHO-rhC7, administered intravenously into new-born C7-null RDEB mice, incorporated into the DEJ of multiple skin sites, tongue and esophagus, restored anchoring fibrils, improved dermal-epidermal adherence, and increased the animals' life span. Furthermore, no circulating or tissue-bound anti-C7 antibodies were observed in the mice. These data demonstrate the efficacy of CHO-rhC7 in a preclinical murine model of RDEB.
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Lin T
authors.initials: LT
authors.lastname: Guey
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Cogan
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hong
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Weihuang
authors.initials: W
authors.lastname: Vivian Ning
authors.affiliation: Shriners Hospital for Children, Portland, Oregon, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Keene
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Kaftan
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Tangarone
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Quinones-Garcia
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA, USA.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.affiliation: Shire, Lexington, Massachussetts, USA.
authors.forename: Omar L
authors.initials: OL
authors.lastname: Francone
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Woodley
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA. Electronic address: chenm@usc.edu.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D024143:Collagen Type VII / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D003412:Cricetulus; D016108:Epidermolysis Bullosa Dystrophica / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D010641:Phenotype; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D024143:Collagen Type VII; D011994:Recombinant Proteins