Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018;7(1):A0070.
doi: 10.5702/massspectrometry.A0070. Epub 2018 Sep 11.

Distribution of Antisense Oligonucleotides in Rat Eyeballs Using MALDI Imaging Mass Spectrometry

Yuko Nakashima  1 , Mitsutoshi Setou  1   2   3
Affiliations

Distribution of Antisense Oligonucleotides in Rat Eyeballs Using MALDI Imaging Mass Spectrometry

Yuko Nakashima et al. Mass Spectrom (Tokyo). 2018.

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.

Keywords: MALDI-IMS; antisense oligonucleotide; distribution; oligonucleotide therapeutics; rat eyeball.

PubMed Disclaimer

Figures

None
Fig. 1. Limit-of-detection (LOD) determination for antisense oligonucleotide (ASO-1).
None
Fig. 2. Measurement of mouse muscle sections washed with organic solvents.
None
Fig. 3. The ion images of ASO-1 in mouse muscle sections.
None
Fig. 4. The ion images of ASO-2 in rat eye sections.
See this image and copyright information in PMC

References

    1. H. Komaki, T. Nagata, T. Saito, S. Masuda, E. Takeshita, M. Sasaki, H. Tachimori, H. Nakamura, Y. Aoki, S. Takeda. Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci. Transl. Med. 10: eaan0713, 2018. - PubMed
    1. M. Matsukura, G. Zon, K. Shinozuka, M. Robert-Guroff, T. Shimada, C. A. Stein, H. Mitsuya, F. Wong-Staal, J. S. Cohen, S. Broder. Regulation of viral expression of human immunodeficiency virus in vitro by an antisense phosphorothioate oligodeoxynucleotide against rev (art/trs) in chronically infected cells. Proc. Natl. Acad. Sci. U.S.A. 86: 4244–4248, 1989. - PMC - PubMed
    1. Y. Takei, K. Kadomatsu, S. Matsuo, H. Itoh, K. Nakazawa, S. Kubota, T. Muramatsu. Antisense oligodeoxynucleotide targeted to midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells. Cancer Res. 61: 8486–8491, 2001. - PubMed
    1. S. M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, T. Tuschl. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494–498, 2001. - PubMed
    1. D. van den Brand, V. Mertens, L. F. A. G. Massuger, R. Brock. siRNA in ovarian cancer—Delivery strategies and targets for therapy. Journal of Controlled Release 283: 45–58, 2018. - PubMed