Evidence map›Paper›PMID 40750796›Full record

ArticleNature communications2025

Discrete Immolative Guanidinium Transporters deliver mRNA to specific organs and red blood cells.

Zhijian Li, Aloysius Ee, Laura Amaya, Jennifer L Hamad, Pavan K Yadav, Sean K Wang, Howard Y Chang, Paul A Wender

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

8 authors.

Zhijian Li *Department of Chemistry, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1849-1672
Aloysius Ee *Department of Chemistry, Stanford University, Stanford, CA, USA.
Laura Amaya *Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8742-9111
Jennifer L HamadDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-0806-6835
Pavan K YadavDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Sean K WangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1557-8510
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9459-4393
Paul A WenderDepartment of Chemistry, Stanford University, Stanford, CA, USA. wenderp@stanford.edu.ORCID http://orcid.org/0000-0001-6319-2829

Funding

New Materials to Deliver mRNA: Applications in Cancer ImmunotherapyR01CA245533 · NCI · STANFORD UNIVERSITY · PI LEVY, RONALD, WAYMOUTH, ROBERT M. · 2020 to 2024
$2.6M
U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA245533
6 · The paper itself

Abstract

RNA medicine is an emerging groundbreaking technology for the prevention and treatment of disease. However, tools to deliver messenger RNA (mRNA) and other polyanions (circRNA, saRNA, pDNA, CRISPR-Cas, reprogramming factors) are required to advance current RNA therapies and address next generation challenges. Existing delivery systems often suffer from laborious syntheses, limited organ selectivity, formulation complexity, and undesired inflammatory responses. Here, we report novel mRNA delivery systems termed Discrete Immolative Guanidinium Transporters (DIGITs), which are synthesized convergently in as few as 4 steps. Unlike most cationic (ammonium) delivery systems, DIGITs are based on cationic guanidinium moieties, which complex mRNA at acidic pH and undergo irreversible neutralization at physiological pH to enable efficient RNA release. Systematic evaluation of structural variations and formulations have led to DIGIT/mRNA complexes that selectively target lung, spleen, and immature red blood cells in peripheral blood in female mice model. DIGIT/mRNA delivery systems show minimal toxicity based on cell viability and biochemical assays, supporting their future utility in biomedical applications.

Indexed as

Drug Delivery SystemsErythrocytesGuanidineRNA, MessengerAnimalsCell SurvivalFemaleHumansLungMiceSpleenGuanidineRNA, Messenger

Identifiers

PMID40750796
PMCPMC12316917

What OpenQuestion holds

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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.