Gene doping - Advances in detection

Brief explanation of the term

September 6, 2010: In light of recent press reports regarding the detection of gene doping, this article aims to provide an overview of the current status of potential detection methods for the various types of gene doping.

Currently, WADA classifies gene doping into two categories.

  1. The use of genetically modified cells (which corresponds, on the one hand, to gene therapy via DNA transfer, and on the other hand, also includes the use of RNA and RNA sequences (e.g., siRNA).
  2. Substances that can cause a change in gene activity (gene expression) (with the examples GW1516 and AICAR).

Gene Doping 1

Perikles Simon’s method (see Publications) addresses the area of Gene Doping 1. The project is funded by WADA and appears to be a promising approach. The method is based on the detection of transgenic DNA molecules (tDNA) that are introduced into muscle cells via viruses. Of course, the method must be validated for doping analysis, which may be initiated by WADA. It is not yet clear how quickly this can be implemented for doping controls.

An example of this type of gene doping is Repoxygen.

Publication: Beiter T, Zimmermann M, Fragasso A, Hudemann J, Niess AM, Bitzer M, Lauer UM, Simon P. Direct and long-term detection of gene doping in conventional blood samples. Gene Ther. 2010 Sep 2, online, doi:10.1038/gt.2010.122

Publication: Beiter T, Zimmermann M, Fragasso A, Armeanu S, Lauer UM, Bitzer M, Su H, Young WL, Niess AM, Simon P. Establishing a novel single-copy primer-internal intron-spanning PCR (spiPCR) procedure for the direct detection of gene doping. Exerc Immunol Rev. 2008;14:73-8

siRNA (small interfering RNA)
In the field of RNA transfer, a potential doping-related application of siRNAs (small interfering RNAs) is being discussed. The first research results on a detection method for siRNAs were published in mid-2010. The online abstract of the publication presents an explanation of a potential doping effect via siRNA.

siRNA (small interfering RNA) consists of short RNA segments of approximately 21–28 nucleotides that play a role in regulating gene expression. They bind to messenger RNA, which is degraded and thus does not undergo translation into the target protein.

Publication: Kohler M, Thomas A, Walpurgis K, Schänzer W, Thevis M. Mass spectrometric detection of siRNA in plasma samples for doping control purposes. Anal Bioanal Chem, (2010) 398:1305-1312.


Gene Doping 2

(Note from April 2, 2013: The doping substances listed under Gene Doping 2 were only listed under Gene Doping until the end of 2011. With the WADA Prohibited List effective from 2012, these substances have been moved to Group S4: Hormones and Metabolic Modulators.)

For the areas covered by Gendoping 2 (GW1516 and AICAR), a mass spectrometric detection method for GW1516 was developed.

 

Publication: Thevis M, Beuck S, Thomas A, Kortner B, Kohler M, Rodchenkov G, Schänzer W.: Doping control analysis of emerging drugs in human plasma - identification of GW501516, S-107, JTV-519, and S-40503. Rapid Commun Mass Spectrom, 23(8) (2009)1139–46. 

Further links:

Encyclopedia article: Gene doping