{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:35:05Z","timestamp":1791891305583,"version":"4.3.4"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JAPAN Anti-Doping Agency","award":["2020 year"],"award-info":[{"award-number":["2020 year"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Despite the World Anti-Doping Agency (WADA) ban on gene doping in the context of advancements in gene therapy, the risk of EPO gene-based doping among athletes is still present. To address this and similar risks, gene-doping tests are being developed in doping control laboratories worldwide. In this regard, the present study was performed with two objectives: to develop a robust gene-doping mouse model with the human EPO gene (hEPO) transferred using recombinant adenovirus (rAdV) as a vector and to develop a detection method to identify gene doping by using this model. The rAdV including the hEPO gene was injected intravenously to transfer the gene to the liver. After injection, the mice showed significantly increased whole-blood red blood cell counts and increased expression of hematopoietic marker genes in the spleen, indicating successful development of the gene-doping model. Next, direct and potentially indirect proof of gene doping were evaluated in whole-blood DNA and RNA by using a quantitative PCR assay and RNA sequencing. Proof of doping could be detected in DNA and RNA samples from one drop of whole blood for approximately a month; furthermore, the overall RNA expression profiles showed significant changes, allowing advanced detection of hEPO gene doping.<\/jats:p>","DOI":"10.3390\/genes12081249","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:27:45Z","timestamp":1629149265000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector"],"prefix":"10.3390","volume":"12","author":[{"given":"Takehito","family":"Sugasawa","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Examination\/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Nakano","sequence":"additional","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1158-9098","authenticated-orcid":false,"given":"Shin-ichiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Examination\/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Research and Development Section, Anicom Specialty Medical Institute Inc., 2-6-3 Chojamachi 5F, Yokohama 231-0033, 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What Is Anti-Doping?. Available online: https:\/\/www.playtruejapan.org\/about\/."},{"key":"ref_2","unstructured":"The World Anti-Doping Agency (WADA) (2021, March 30). Who We Are?. Available online: https:\/\/www.wada-ama.org\/en\/who-we-are."},{"key":"ref_3","unstructured":"The World Anti-Doping Agency (WADA) (2021). The World Anti-Doping Code International Standard Prohibited List 2021, WADA."},{"key":"ref_4","unstructured":"The World Anti-Doping Agency (WADA) (2021). World Anti-Doping Code 2021, WADA."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sugasawa, T., Aoki, K., Watanabe, K., Yanazawa, K., Natsume, T., Takemasa, T., Yamaguchi, K., Takeuchi, Y., Aita, Y., and Yahagi, N. (2019). Detection of Transgenes in Gene Delivery Model Mice by Adenoviral Vector Using ddPCR. Genes, 10.","DOI":"10.20944\/preprints201904.0285.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e8595","DOI":"10.7717\/peerj.8595","article-title":"The detection of trans gene fragments of hEPO in gene doping model mice by Taqman qPCR assay","volume":"8","author":"Aoki","year":"2020","journal-title":"PeerJ"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sugasawa, T., Aoki, K., Yanazawa, K., and Takekoshi, K. (2020). Detection of multiple transgene fragments in a mouse model of gene doping based on plasmid vector using TaqMan-qPCR assay. Genes, 11.","DOI":"10.20944\/preprints202005.0366.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e3108","DOI":"10.1002\/jgm.3108","article-title":"Clinical translation of gene medicine","volume":"21","author":"Wang","year":"2019","journal-title":"J. Gene Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-020-2608-y","article-title":"ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques","volume":"586","author":"Lambe","year":"2020","journal-title":"Nature"},{"key":"ref_11","unstructured":"The World Anti-Doping Agency (WADA) (2021). Gene Doping Detection Based on Polymerase Chain Reaction (PCR), WADA."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/bcp.12034","article-title":"Erythropoietin doping in cycling: Lack of evidence for efficacy and a negative risk-benefit: Erythropoietin doping in cycling","volume":"75","author":"Heuberger","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1080\/09523367.2013.879858","article-title":"Why Lance Armstrong? Historical context and key turning points in the \u2018Cleaning Up\u2019 of professional cycling","volume":"31","author":"DiMeo","year":"2014","journal-title":"Int. J. Hist. Sport"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.csm.2009.06.005","article-title":"The status of doping and drug use and the implications for boxing","volume":"28","author":"Wadler","year":"2009","journal-title":"Clin. Sports Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"257","DOI":"10.7861\/clinmedicine.12-3-257","article-title":"Proscribed drugs at the Olympic Games: Permitted use and misuse (doping) by athletes","volume":"12","author":"Fitch","year":"2012","journal-title":"Clin. Med."},{"key":"ref_16","first-page":"3","article-title":"Analytical study of doping cases of banned substances during Olympics games from 1968 to 2012","volume":"3","author":"Sharma","year":"2016","journal-title":"Int. J. Phys. Educ. Sports Health"},{"key":"ref_17","unstructured":"Wiley (2021, March 30). Gene Therapy Trials Worldwide. Available online: https:\/\/a873679.fmphost.com\/fmi\/webd\/GTCT."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tozaki, T., Ohnuma, A., Takasu, M., Kikuchi, M., Kakoi, H., Hirota, K.-I., Kusano, K., and Nagata, S.-I. (2019). Droplet digital pcr detection of the erythropoietin transgene from horse plasma and urine for gene-doping control. Genes, 10.","DOI":"10.3390\/genes10030243"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tozaki, T., Gamo, S., Takasu, M., Kikuchi, M., Kakoi, H., Hirota, K.-I., Kusano, K., and Nagata, S.-I. (2018). Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: A model case study for gene doping detection. BMC Res. Notes, 11.","DOI":"10.1186\/s13104-018-3815-6"},{"key":"ref_20","unstructured":"The World Anti-Doping Agency (WADA) (2021). Athlete Biological Passport (ABP) Operating Guidelines, WADA."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbrc.2007.08.165","article-title":"In Vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression","volume":"363","author":"Takeuchi","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1016\/j.celrep.2016.07.069","article-title":"KLF15 enables rapid switching between lipogenesis and gluconeogenesis during fasting","volume":"16","author":"Takeuchi","year":"2016","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1006\/viro.2002.1406","article-title":"Evaluation of accuracy and precision of adenovirus absorptivity at 260 nm under conditions of complete DNA disruption","volume":"295","author":"Sweeney","year":"2002","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/gt.2010.49","article-title":"Gene doping detection: Evaluation of approach for direct detection of gene transfer using erythropoietin as a model system","volume":"17","author":"Baoutina","year":"2010","journal-title":"Gene Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/dta.1347","article-title":"Detection of EPO gene doping in blood: Detection of EPO gene doping in blood","volume":"4","author":"Neuberger","year":"2012","journal-title":"Drug Test. Anal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Su, W., Sun, J., Shimizu, K., and Kadota, K. (2019). TCC-GUI: A Shiny-based application for differential expression analysis of RNA-Seq count data. BMC Res. Notes, 12.","DOI":"10.1186\/s13104-019-4179-2"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1093\/bioinformatics\/bty890","article-title":"TissueEnrich: Tissue-specific gene enrichment analysis","volume":"35","author":"Jain","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/iub.2177","article-title":"GATA1 mutations in red cell disorders","volume":"72","author":"Ling","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/17474086.2018.1436965","article-title":"GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders: Consequences for therapy","volume":"11","author":"Ling","year":"2018","journal-title":"Expert Rev. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-020-06849-8","article-title":"Structural variation of the malaria-associated human glycophorin A-B-E region","volume":"21","author":"Louzada","year":"2020","journal-title":"BMC Genom."},{"key":"ref_34","first-page":"151","article-title":"Complex signatures of natural selection at GYPA","volume":"137","author":"Bigham","year":"2018","journal-title":"Qual. Life Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1172\/JCI133344","article-title":"Enasidenib drives human erythroid differentiation independently of isocitrate dehydrogenase 2","volume":"130","author":"Dutta","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_36","first-page":"49","article-title":"Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy","volume":"19","author":"Powell","year":"2015","journal-title":"Discov. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41591-020-01179-4","article-title":"Oxford COVID Vaccine Trial Group. Phase 1\/2 Trial of SARS-CoV-2 Vaccine ChAdOx1 NCoV-19 with a Booster Dose Induces Multifunctional Antibody Responses","volume":"27","author":"Barrett","year":"2021","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-020-01194-5","article-title":"Oxford COVID Vaccine Trial Group. T Cell and Antibody Responses Induced by a Single Dose of ChAdOx1 NCoV-19 (AZD1222) Vaccine in a Phase 1\/2 Clinical Trial","volume":"27","author":"Ewer","year":"2021","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2009\/476217","article-title":"A human hepatocyte-bearing mouse: An animal model to predict drug metabolism and effectiveness in humans","volume":"2009","author":"Yoshizato","year":"2009","journal-title":"PPAR Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.trac.2011.01.019","article-title":"Point-of-care testing (POCT): Current techniques and future perspectives","volume":"30","author":"Luppa","year":"2011","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1007\/s00216-018-0931-z","article-title":"Inhibition mechanisms of hemoglobin, immunoglobulin G, and whole blood in digital and real-time PCR","volume":"410","author":"Sidstedt","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Marchand, A., Roulland, I., Semence, F., and Ericsson, M. (2021). EPO transgene detection in dried blood spots for antidoping application. Drug Test. Anal., online ahead of print.","DOI":"10.1002\/dta.3059"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1423-0410.2007.00970.x","article-title":"Functions of red cell surface proteins","volume":"93","author":"Daniels","year":"2007","journal-title":"Vox Sang."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1016\/j.celrep.2019.05.046","article-title":"Transcriptional states and chromatin accessibility underlying human erythropoiesis","volume":"27","author":"Ludwig","year":"2019","journal-title":"Cell Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6258","DOI":"10.1182\/blood-2011-07-356006","article-title":"From stem cell to red cell: Regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications","volume":"118","author":"Hattangadi","year":"2011","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1097\/00005768-200007000-00009","article-title":"Effect of rhEPO administration on serum levels of sTfR and cycling performance","volume":"32","author":"Birkeland","year":"2000","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1101\/gad.1627208","article-title":"Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis","volume":"22","author":"Sankaran","year":"2008","journal-title":"Genes Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.exphem.2020.06.006","article-title":"Enhancing mitochondrial function in vivo rescues MDS-like anemia induced by pRb deficiency","volume":"88","author":"Sen","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.lab.2005.10.005","article-title":"The peripheral blood transcriptome dynamically reflects system wide biology: A potential diagnostic tool","volume":"147","author":"Liew","year":"2006","journal-title":"J. Lab. Clin. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cll.2007.10.009","article-title":"Data mining for biomarker development: A review of tissue specificity analysis","volume":"28","author":"Klee","year":"2008","journal-title":"Clin. Lab. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Prassas, I., Chrystoja, C.C., Makawita, S., and Diamandis, E. (2012). Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery. BMC Med., 10.","DOI":"10.1186\/1741-7015-10-39"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ygeno.2007.06.010","article-title":"Differential gene expression during terminal erythroid differentiation","volume":"90","author":"Koury","year":"2007","journal-title":"Genomics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1128\/MCB.22.12.4158-4166.2002","article-title":"Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is essential for embryonic development","volume":"22","author":"Sirois","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.stemcr.2020.06.018","article-title":"Mthfd2 modulates mitochondrial function and DNA repair to maintain the pluripotency of mouse stem cells","volume":"15","author":"Yue","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"658","DOI":"10.3389\/fonc.2020.00658","article-title":"More than a metabolic enzyme: MTHFD2 as a novel target for anticancer therapy?","volume":"10","author":"Zhu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Maragno, A.L., Pironin, M., Alcalde, H., Cong, X., Knobeloch, K.-P., Tangy, F., Zhang, D.-E., Ghysdael, J., and Quang, C.T. (2011). ISG15 Modulates development of the erythroid lineage. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026068"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1152\/physiolgenomics.00108.2015","article-title":"Blood transcriptional signature of recombinant human erythropoietin administration and implications for antidoping strategies","volume":"48","author":"Durussel","year":"2016","journal-title":"Physiol. Genom."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wang, G., Durussel, J., Shurlock, J., Mooses, M., Fuku, N., Bruinvels, G., Pedlar, C., Burden, R., Murray, A., and Yee, B. (2017). Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4191-7"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Loria, F., Cox, H.D., Voss, S.C., Rocca, A., Miller, G.D., Townsend, N., Georgakopoulos, C., Eichner, D., Kuuranne, T., and Leuenberger, N. (2021). The use of RNA-based 5\u2032-aminolevulinate synthase 2 biomarkers in dried blood spots to detect recombinant human erythropoietin microdoses. Drug Test. Anal., online ahead of print.","DOI":"10.1002\/dta.3123"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nbt.3758","article-title":"Robotic crowd biology with Maholo LabDroids","volume":"35","author":"Yachie","year":"2017","journal-title":"Nat. Biotechnol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1249\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:47:12Z","timestamp":1760165232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,16]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["genes12081249"],"URL":"https:\/\/doi.org\/10.3390\/genes12081249","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202107.0034.v1","asserted-by":"object"}]},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,16]]}}}