{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:16:15Z","timestamp":1793301375009,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis, but is not the only player with an angiogenic function. Fibroblast growth factor-2 (FGF2), which was discovered before VEGF, is also an angiogenic growth factor. It has been shown that FGF2 plays positive pathophysiological roles in tissue remodeling, bone health, and regeneration, such as the repair of neuronal damage, skin wound healing, joint protection, and the control of hypertension. Targeting FGF2 as a therapeutic tool in disease treatment through clinically useful inhibitors has not been developed until recently. An isolated inhibitory RNA aptamer against FGF2, named RBM-007, has followed an extensive preclinical study, with two clinical trials in phase 2 and phase 1, respectively, underway to assess the therapeutic impact in age-related macular degeneration (wet AMD) and achondroplasia (ACH), respectively. Moreover, showing broad therapeutic potential, preclinical evidence supports the use of RBM-007 in the treatment of lung cancer and cancer pain.<\/jats:p>","DOI":"10.3390\/cells10071617","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T11:45:40Z","timestamp":1624880740000},"page":"1617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Multiple Therapeutic Applications of RBM-007, an Anti-FGF2 Aptamer"],"prefix":"10.3390","volume":"10","author":[{"given":"Yoshikazu","family":"Nakamura","sequence":"first","affiliation":[{"name":"Division of RNA Medical Science, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"},{"name":"RIBOMIC Inc., Tokyo 108-0071, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/humu.21067","article-title":"Molecular pathology of the fibroblast growth factor family","volume":"30","author":"Krejci","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/08977194.2012.656761","article-title":"FGF\/FGFR signaling in bone formation: Progress and perspectives","volume":"30","author":"Marie","year":"2012","journal-title":"Growth Factors"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S1357-2725(99)00133-8","article-title":"Fibroblast growth factor-2","volume":"32","author":"Thiery","year":"2000","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bbrc.2007.11.140","article-title":"FGF-2 signaling induces downregulation of TAZ protein in osteoblastic MC3T3-E1 cells","volume":"366","author":"Eda","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1210\/jcem.86.2.7199","article-title":"Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2","volume":"86","author":"Kawaguchi","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1006\/bbrc.1999.1601","article-title":"Basic fibroblast growth factor induces osteoclast formation by reciprocally regulating the production of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in mouse osteoblastic cells","volume":"265","author":"Nakagawa","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1359\/jbmr.2000.15.3.466","article-title":"Direct and indirect actions of fibroblast growth factor 2 on osteoclastic bone resorption in cultures","volume":"15","author":"Kawaguchi","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9911","DOI":"10.1073\/pnas.86.24.9911","article-title":"Monoclonal antibodies against heparin-binding growth factor II\/basic fibroblast growth factor that block its biological activity: Invalidity of the antibodies for tumor angiogenesis","volume":"86","author":"Matsuzaki","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3109\/08977199909002126","article-title":"Development of novel monoclonal antibodies for the analysis of functional sites in FGF-2","volume":"16","author":"Rege","year":"1999","journal-title":"Growth Factors"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.lungcan.2003.11.005","article-title":"Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines","volume":"44","author":"Kuhn","year":"2004","journal-title":"Lung Cancer"},{"key":"ref_11","first-page":"6180","article-title":"Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor","volume":"51","author":"Hori","year":"1991","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1158\/1535-7163.MCT-11-0813","article-title":"A novel monoclonal antibody to fibroblast growth factor 2 effectively inhibits growth of hepatocellular carcinoma xenografts","volume":"11","author":"Wang","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1038\/mt.2016.158","article-title":"Dual therapeutic action of a neutralizing anti-FGF2 aptamer in bone diseases and bone cancer pain","volume":"24","author":"Jin","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrd3141","article-title":"Aptamers as therapeutics","volume":"9","author":"Keefe","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ajo.2015.04.003","article-title":"Incidence of late-stage age-related macular degeneration in american whites: Systematic review and meta-analysis","volume":"160","author":"Rudnicka","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0002-9440(10)65138-3","article-title":"Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris","volume":"155","author":"Blaauwgeers","year":"1990","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/nat.2015.0573","article-title":"Fit for the eye: Aptamers in ocular disorders","volume":"26","author":"Drolet","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1056\/NEJMoa062655","article-title":"Ranibizumab versus verteporfin for neovascular age-related macular degeneration","volume":"355","author":"Brown","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eaao4097","DOI":"10.1126\/scitranslmed.aao4097","article-title":"A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration","volume":"10","author":"Kashani","year":"2018","journal-title":"Sci. Trans. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1016\/j.ophtha.2013.03.046","article-title":"Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON a multicenter cohort study (SEVEN-UP)","volume":"120","author":"Rofagha","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.ophtha.2012.09.006","article-title":"VIEW 1 and VIEW 2 study groups: Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration","volume":"119","author":"Heier","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.ophtha.2012.03.053","article-title":"Comparison of age-related macular degeneration treatments trials (CATT) research group: Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: Two-year results","volume":"119","author":"Martin","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ophtha.2013.10.019","article-title":"Risk of scar in the comparison of age-related macular degeneration treatments trials","volume":"121","author":"Daniel","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1097\/IAE.0b013e318240a516","article-title":"Causes of unsuccessful ranibizumab treatment in exudative age-related macular degeneration in clinical settings","volume":"32","author":"Cohen","year":"2012","journal-title":"Retina"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.cytogfr.2005.01.004","article-title":"Fibroblast growth factor\/fibroblast growth factor receptor system in angiogenesis","volume":"16","author":"Presta","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_28","first-page":"70","article-title":"Neovascular growth factors","volume":"1","author":"Schultz","year":"1991","journal-title":"Eye"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1755-3768.1990.tb01668.x","article-title":"Occurrence of drusen, pigmentary changes and exudative changes in the macula with reference to age-related macular degeneration an epidemiological study of 1000 aged individuals","volume":"68","author":"Vinding","year":"1990","journal-title":"Acta Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/hh1101.091191","article-title":"Vascular endothelial growth factor and basic fibroblast growth factor differentially modulate early postnatal coronary angiogenesis","volume":"88","author":"Tomanek","year":"2001","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1046\/j.1365-2362.2003.01223.x","article-title":"Basic fibrobrast growth factor induces the secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not by endothelial cells","volume":"33","author":"Belgore","year":"2003","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1161\/CIRCRESAHA.107.168682","article-title":"Activation transcription factor-4 induced by fibroblast growth factor-2 regulates vascular endothelial growth factor-A transcription in vascular smooth muscle cells and mediates intimal thickening in rat arteries following balloon injury","volume":"103","author":"Malabanan","year":"2008","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nm848","article-title":"Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2","volume":"9","author":"Cao","year":"2003","journal-title":"Nat. Med."},{"key":"ref_34","first-page":"e51375","article-title":"The corneal micropocket assay: A model of angiogenesis in the mouse eye","volume":"90","author":"Birsner","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1046\/j.1523-1755.2002.00333.x","article-title":"Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation","volume":"61","author":"Strutz","year":"2002","journal-title":"Kidney Int."},{"key":"ref_36","first-page":"1975","article-title":"Transforming growth factor-beta1, -beta2, and -beta3 in vivo: Effects on normal and mitomycin C-modulated conjunctival scarring","volume":"40","author":"Cordeiro","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1007\/s00417-011-1730-9","article-title":"The novel use of decorin in prevention of the development of proliferative vitreoretinopathy (PVR)","volume":"249","author":"Nassar","year":"2011","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/sj.gt.3301865","article-title":"Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome","volume":"10","author":"Cordeiro","year":"2003","journal-title":"Gene Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1096\/fj.13-229740","article-title":"Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy","volume":"28","author":"Ishikawa","year":"2014","journal-title":"FASEB J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.omtn.2019.07.018","article-title":"Anti-angiogenic and anti-scarring dual action of an anti-fibroblast growth factor 2 aptamer in animal models of retinal disease","volume":"17","author":"Matsuda","year":"2019","journal-title":"Mol. Ther. Nucl. Acids"},{"key":"ref_41","unstructured":"(2018, August 16). U.S. National Library Medicine, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03633084."},{"key":"ref_42","unstructured":"(2019, December 16). U.S. National Library Medicine, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT04200248."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/jmg.23.4.328","article-title":"The birth prevalence rates for the skeletal dysplasias","volume":"23","author":"Orioli","year":"1986","journal-title":"J. Med. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/jb\/mvq121","article-title":"Fibroblast growth factors: From molecular evolution to roles in development, metabolism and disease","volume":"149","author":"Itoh","year":"2011","journal-title":"J. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/mgg3.96","article-title":"FGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia Registry","volume":"2","author":"Xue","year":"2014","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"30103","DOI":"10.1074\/jbc.M109.094086","article-title":"Physical basis behind achondroplasia, the most common form of human dwarfism","volume":"285","author":"He","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/dvdy.24479","article-title":"Achondroplasia: Development, pathogenesis, and therapy","volume":"246","author":"Ornitz","year":"2017","journal-title":"Dev. Dyn."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1172\/JCI83926","article-title":"Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model","volume":"126","author":"Dambroise","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_49","first-page":"123","article-title":"Growth Hormone Treatment for Achondroplasia","volume":"16","author":"Yorifuji","year":"2018","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/hmg\/ddv441","article-title":"Multikinase activity of fibroblast growth factor receptor (FGFR) inhibitors SU5402, PD173074, AZD1480, AZD4547 and BGJ398 compromises the use of small chemicals targeting FGFR catalytic activity for therapy of short-stature syndromes","volume":"25","author":"Gudernova","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eaba4226","DOI":"10.1126\/scitranslmed.aba4226","article-title":"RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia","volume":"13","author":"Kimura","year":"2021","journal-title":"Sci. Trans. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1056\/NEJMoa1813446","article-title":"C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia","volume":"381","author":"Savarirayan","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1124\/jpet.114.218560","article-title":"Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism","volume":"353","author":"Wendt","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ymgme.2007.06.014","article-title":"C-natriuretic peptide: An important regulator of cartilage","volume":"92","author":"Pejchalova","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_55","unstructured":"(2021, May 12). Japic Clinical Trials Information. Available online: https:\/\/www.clinicaltrials.jp\/cti-user\/trial\/ShowDirect.jsp?directLink=0p52SZqEULFxxBQ0QuD.Vg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0169-409X(03)00098-X","article-title":"Animal and cellular models of chronic pain","volume":"55","author":"Wang","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1083\/jcb.141.7.1659","article-title":"Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An Autocrine mechanism contributing to angiogenesis","volume":"141","author":"Seghezzi","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1111\/j.1460-9568.1997.tb01483.x","article-title":"FGF-2 induces nerve growth factor expression in cultured rat hippocampal neurons","volume":"9","author":"Ferhat","year":"1997","journal-title":"Eur. J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1460-9568.1990.tb00382.x","article-title":"Regulation of nerve growth factor (NGF) synthesis in the rat central nervous system: Comparison between the effects of interleukin-I and various growth factors in astrocyte cultures and in vivo","volume":"2","author":"Spranger","year":"1990","journal-title":"Eur. J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.bbamcr.2012.01.004","article-title":"Mechanisms of FGFR-mediated carcinogenesis","volume":"1823","author":"Ahmad","year":"2012","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtho.2015.08.003","article-title":"FGFR Signaling as a Target for Lung Cancer Therapy","volume":"11","author":"Desai","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.bbrc.2018.07.044","article-title":"FGF2 aptamer inhibits the growth of FGF2-FGFR pathway driven lung cancer cells","volume":"503","author":"Hamamoto","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7822","DOI":"10.1093\/nar\/gkq615","article-title":"Conformational plasticity of RNA for target recognition as revealed by the 2.15 \u00c5 crystal structure of a human IgG-aptamer complex","volume":"38","author":"Nomura","year":"2010","journal-title":"Nucl. Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.biochi.2017.10.006","article-title":"Aptamers as therapeutic middle molecules","volume":"145","author":"Nakamura","year":"2018","journal-title":"Biochimie"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13379","DOI":"10.1073\/pnas.1324235111","article-title":"Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis","volume":"111","author":"Oladipupo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"107775","DOI":"10.1016\/j.exer.2019.107775","article-title":"FGF2-induced STAT3 activation regulates pathologic neovascularization","volume":"187","author":"Dong","year":"2019","journal-title":"Exp. Eye Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:01Z","timestamp":1760163961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,28]]},"references-count":66,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cells10071617"],"URL":"https:\/\/doi.org\/10.3390\/cells10071617","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,28]]}}}