Evidence map›Paper›PMID 42372149›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

A nucleic acid labeling chemistry reveals surface DNA on exosomes.

Filip Bošković, Priyanka Dutta Gupta, Jian Zhang, Yamuna Krishnan, Jack W Szostak

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Nanopore-Based Profiling of PEGylation in Nucleic Acid Therapeutics.Journal of the American Chemical Society · 2026
    Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Filip Bošković *HHMI, The University of Chicago, Chicago, IL 60637.ORCID 0000-0001-7663-2408
Priyanka Dutta Gupta *Department of Chemistry, The University of Chicago, Chicago, IL 60637.
Jian ZhangHHMI, The University of Chicago, Chicago, IL 60637.ORCID 0000-0001-8799-3444
Yamuna KrishnanDepartment of Chemistry, The University of Chicago, Chicago, IL 60637.ORCID 0000-0001-5282-8852
Jack W SzostakHHMI, The University of Chicago, Chicago, IL 60637.ORCID 0000-0003-4131-1203

Funding

Intracellular Electrophysiology: An electrochemical atlas of organellesDP1GM149751 · NIGMS · UNIVERSITY OF CHICAGO · PI KRISHNAN, YAMUNA · 2022 to 2025
$5.7M
Mechanism and function of intracellular sodium-proton exchangersR01GM147197 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KRISHNAN, YAMUNA, MIRSHAHI, TOORAJ · 2022 to 2025
$2.4M
Calcium homeostasis in organellesR01NS112139 · NINDS · UNIVERSITY OF CHICAGO · PI KRISHNAN, YAMUNA · 2020 to 2024
$1.8M
European Molecular Biology Organization (EMBO) ALTF 106-2023HHMI (HHMI) InvestigatorHHS | NIH (NIH) 1R01GM147197-01HHS | NIH (NIH) 1R01NS112139-01A1HHS | NIH (NIH) DP1GM149751Human Frontier Science Program (HFSP) RGP0032/2022NIGMS NIH HHS DP1 GM149751NIGMS NIH HHS R01 GM147197NINDS NIH HHS R01 NS112139
6 · The paper itself

Abstract

Chemical labeling of nucleic acids is essential to pinpoint the structure, localization, and function of RNA and DNA. Yet, reversible sequence-independent chemistries that can label native RNA and DNA remain poorly developed. Here, we describe Reversible Uridine Nitrilium-mediated Addition (RUNA), a reversible covalent chemistry that selectively modifies uridine and thymidine residues via N3 deprotonation and reaction with a nitrilium ion intermediate generated from an aldehyde and an isonitrile. The reaction forms a stable N3 adduct that can be quantitatively reversed by hydrolysis. By using reagents that are either membrane permeable or impermeable, we demonstrate the localization and function of DNA on exosomes. Although exosomes harbor nucleic acids, whether the latter are encapsulated in the exosome lumen or are surface-adhered is unknown. RUNA revealed that exosomes display DNA on their outer surface. The abundance of such surface DNA increases upon DNA-damage accumulation in cancer cells that are treated with a PARP inhibitor. This surface DNA drives exosome uptake by M2-polarized macrophages through scavenger receptors and triggers a shift toward an M1-like proinflammatory state. The selective labeling of surface DNA revealed an unexpected mechanism by which exosomes engage innate immune cells. RUNA is a versatile tool to analyze the nucleic acid content and functionality of extracellular vesicles in health and disease.

Indexed as

DNAExosomesNucleic AcidsAnimalsDNA DamageHumansMacrophagesStaining and LabelingUridineDNANucleic AcidsUridineexosomesnucleic acid chemical labelingnucleic acid chemistrysurface DNA

Identifiers

PMID42372149
PMCPMC13343009

What OpenQuestion holds

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Registered trials

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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.