title: Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.
abstract: Osteoarthritis (OA) is a chronic degenerative joint disease and a major health problem in the elderly population. No disease-modifying osteoarthritis drug (DMOAD) has been made available for clinical use. Here we present a disease-modifying strategy for OA, focusing on messenger RNA (mRNA) delivery of a therapeutic transcription factor using polyethylene glycol (PEG)-polyamino acid block copolymer-based polyplex nanomicelles. When polyplex nanomicelles carrying the cartilage-anabolic, runt-related transcription factor (RUNX) 1 mRNA were injected into mouse OA knee joints, OA progression was significantly suppressed compared with the non-treatment control. Expressions of cartilage-anabolic markers and proliferation were augmented in articular chondrocytes of the RUNX1-injected knees. Thus, this study provides a proof of concept of the treatment of degenerative diseases such as OA by the in situ mRNA delivery of therapeutic transcription factors; the presented approach will directly connect basic findings on disease-protective or tissue-regenerating factors to disease treatment.
authors.affiliation: Department of Bioengineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Hailati
authors.initials: H
authors.lastname: Aini
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Itaka
authors.affiliation: Department of Bioengineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Fujisawa
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Materials Engineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Department of Materials Engineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Bone and Cartilage Regenerative Medicine and Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Bioengineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ung-il
authors.initials: UI
authors.lastname: Chung
authors.affiliation: Department of Bioengineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ohba
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D007270:Injections, Intra-Articular; D051379:Mice; D008823:Micelles; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D008823:Micelles; D012333:RNA, Messenger; D014157:Transcription Factors