Evidence map›Paper›PMID 33275144›Full record

ArticleNucleic acids research2021

High-resolution visualization and quantification of nucleic acid-based therapeutics in cells and tissues using Nanoscale secondary ion mass spectrometry (NanoSIMS).

Cuiwen He, Michael T Migawa, Kai Chen, Thomas A Weston, Michael Tanowitz, Wenxin Song, Paul Guagliardo, K Swaminathan Iyer, C Frank Bennett, Loren G Fong and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Article
  6. Article
  7. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
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  10. Article
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  13. Article
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  16. Article
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  19. Review
  20. Tool to Resolve Distortions in Elemental and Isotopic Imaging.Journal of the American Chemical Society · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Cuiwen HeDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Michael T MigawaIonis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Kai ChenSchool of Molecular Sciences, University of Western Australia, Perth 6009, Australia.
Thomas A WestonDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Michael TanowitzIonis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Wenxin SongDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Paul GuagliardoCentre for Microscopy, Characterisation and Analysis, University of Western Australia, Perth 6009, Australia.
K Swaminathan IyerSchool of Molecular Sciences, University of Western Australia, Perth 6009, Australia.
C Frank BennettIonis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Loren G FongDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Punit P SethIonis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Stephen G YoungDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Haibo JiangSchool of Molecular Sciences, University of Western Australia, Perth 6009, Australia.
University of California, Los Angeles · USIonis Pharmaceuticals (United States) · USThe University of Western Australia · AU

Funding

The Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3M
Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2019 to 2023
$11.7M
Refining Physiologic Mechanisms for Intravascular Triglyceride MetabolismR01HL087228 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEIGNEUX, ANNE, FONG, LOREN GI · 2007 to 2024
$7.8M
Investigating Mechanisms for Lipid Transport in Health and DiseaseR35HL139725 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2018 to 2024
$6.1M
Defining mechanisms for lipid transport across capillary endothelial cellsR01HL125335 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2015 to 2017
$1.2M
NHLBI NIH HHS P01 HL090553NHLBI NIH HHS P01 HL146358NHLBI NIH HHS R01 HL087228NHLBI NIH HHS R01 HL125335NHLBI NIH HHS R35 HL139725
6 · The paper itself

Abstract

Nucleic acid therapeutics (NATs) have proven useful in promoting the degradation of specific transcripts, modifying gene expression, and regulating mRNA splicing. In each situation, efficient delivery of nucleic acids to cells, tissues and intracellular compartments is crucial-both for optimizing efficacy and reducing side effects. Despite successes in NATs, our understanding of their cellular uptake and distribution in tissues is limited. Current methods have yielded insights into distribution of NATs within cells and tissues, but the sensitivity and resolution of these approaches are limited. Here, we show that nanoscale secondary ion mass spectrometry (NanoSIMS) imaging can be used to define the distribution of 5-bromo-2'-deoxythymidine (5-BrdT) modified antisense oligonucleotides (ASO) in cells and tissues with high sensitivity and spatial resolution. This approach makes it possible to define ASO uptake and distribution in different subcellular compartments and to quantify the impact of targeting ligands designed to promote ASO uptake by cells. Our studies showed that phosphorothioate ASOs are associated with filopodia and the inner nuclear membrane in cultured cells, and also revealed substantial cellular and subcellular heterogeneity of ASO uptake in mouse tissues. NanoSIMS imaging represents a significant advance in visualizing uptake and distribution of NATs; this approach will be useful in optimizing efficacy and delivery of NATs for treating human disease.

Indexed as

3T3-L1 CellsAcetylgalactosamineAnimalsAsialoglycoprotein ReceptorCesiumHEK293 CellsHeLa CellsHumansKidneyLiverMaleMiceMice, Inbred C57BLMicroscopy, ElectronMyocardiumOligonucleotides, AntisenseAcetylgalactosamineAsialoglycoprotein ReceptorCesiumMALAT1 long non-coding RNA, humanOligonucleotides, AntisensePhosphorothioate OligonucleotidesRNA, Long NoncodingSulfursulfur-32Sulfur-34Sulfur Isotopes

Identifiers

PMID33275144
PMCPMC7797060
OpenAlexW3109433756

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.