Tritium labeling of antisense oligonucleotides via different conjugation agents

Martin Edelmann, Christophe Husser, Martina B. Duschmalé, Guy Fischer, Claudia Senn, Erich Koller, Andreas Brink

Research output: Contribution to journalReview articlepeer-review


A novel approach to tritium-labeled antisense oligonucleotides (ASO) was established by conjugating N-succinimidyl propionate, as well as maleimide-derivatives, to the 3′-end of ASOs targeting metastasis-associated lung adenocarcinoma transcript 1 (Malat1) containing amino- or sulfhydryl-linkers. In vitro stability and Malat1 RNA reduction studies demonstrated that N-ethylmaleimide (NEM) could be used as a stable tag while maintaining the desired target interaction. The corresponding radioactive label conjugation using [3H]-NEM resulted in tritium-labeled ASOs with a high molar specific activity of up to 17 Ci/mmol. Single-dose in vivo studies in mice were carried out to compare [3H]-ASOs with their unlabeled counterpart ASOs, with and without conjugation to N-acetylgalactosamine (GalNAc), for tissue and plasma concentrations time profiles. Despite the structural modification of the labeled ASOs, in vitro target interaction and in vivo pharmacokinetic behaviors were similar to that of the unlabeled ASOs. In conclusion, this new method provides a powerful technique for fast and safe access to tritium-labeled oligonucleotides, e.g., for pharmacokinetic, mass balance, or autoradiography studies.
Original languageEnglish
Article number4 (2021)
JournalAAPS Open
Publication statusPublished - 15 Nov 2021


  • Antisense oligonucleotide
  • Radiolabeling
  • Malat1
  • Pharmacokinetics
  • Tritium


Dive into the research topics of 'Tritium labeling of antisense oligonucleotides via different conjugation agents'. Together they form a unique fingerprint.

Cite this