Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector

Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector / Takehito Sugasawa, Takuro Nakano, Shin-Ichiro Fujita, Yuki Matsumoto, Genki Ishihara, Kai Aoki, Koki Yanazawa, Seiko Ono, Shinsuke Tamai, Lev Manevich, Haruna Ueda, Noriyo Ishibashi, Kenshirou Tamai, Yasuharu Kanki, Yasuko Yoshida, Koichi Watanabe, Tohru Takemasa, Yasushi Kawakami, Kazuhiro Takekoshi. - (Genes 12 (2021) 8 (16 August); 1249)

  • PMID: 34440425
  • PMCID: PMC8392868
  • DOI: 10.3390/genes12081249


Abstract

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.

Original document

Parameters

Science
Study
Date
16 August 2021
People
Aoki, Kai
Fujita, Shin-Ichiro
Ishibashi, Noriyo
Ishihara, Genki
Kanki, Yasuharu
Kawakami, Yasushi
Manevich, Lev
Matsumoto, Yuki
Nakano, Takuro
Ono, Seiko
Sugasawa, Takehito
Takekoshi, Kazuhiro
Takemasa, Tohru
Tamai, Kenshirou
Tamai, Shinsuke
Ueda, Haruna
Watanabe, Koichi
Yanazawa, Koki
Yoshida, Yasuko
Country
Japan
Language
English
Other organisations
Tsukuba International University
University of Tsukuba
Analytical aspects
DNA analysis
Testing method development
Doping classes
M3. Gene And Cell Doping
S2. Peptide Hormones, Growth Factors
Substances
Erythropoietin (EPO)
Medical terms
Gene Therapy
Document category
Scientific article
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Pdf file
Date generated
30 August 2021
Date of last modification
1 September 2021
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  • ADRV
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  • Sport/IFs
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  • Laboratories
  • Analytical aspects
  • Doping classes
  • Substances
  • Medical terms
  • Various
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