Mass Spectrometry
Online ISSN : 2186-5116
Print ISSN : 2187-137X
Original Article
Distribution of Antisense Oligonucleotides in Rat Eyeballs Using MALDI Imaging Mass Spectrometry
Yuko NakashimaMitsutoshi Setou
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2018 Volume 7 Issue 1 Pages A0070

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Abstract

Oligonucleotide-based therapeutics such as antisense oligonucleotides, small interfering RNAs (siRNAs), decoy and aptamer have been extensively developed. To investigate the pharmacokinetics of oligonucleotide therapeutics, it is common to label a radioisotope in a nucleic acid and visualize it. However, if the labeled terminal nucleotide is decomposed by a nuclease in vivo, only the labeled nucleotide is detected, and it is impossible to observe the nucleic acid exhibiting the drug effect. The distribution of biomolecules, such as phospholipids, proteins, and glycolipids, can be obtained and visualized without labeling using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). MALDI-IMS is also used in pharmacokinetic analysis to visualize a parent drug and its metabolites simultaneously. In this study, we reported a methodology for oligonucleotides analysis by MALDI-IMS. When phosphorothioate antisense oligonucleotide was administered into the eyeball of rats, it reached the retina after 30 min without undergoing decomposition by nucleases.

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© 2018 Yuko Nakashima and Mitsutoshi Setou. This is an open access article distributed under the terms of Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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