Evidence map›Paper›PMID 41545029›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

A Systemic Selective Modified mRNA Delivery Platform for Preventing Chemotherapy-Induced Cardiotoxicity.

Jimeen Yoo, Gayatri Mainkar, Matteo Ghiringhelli, Bernardo Gindri Dos Santos, Magdalena M Żak, Keerat Kaur, Ann Anu Kurian, Matthew Adjmi, Segev Sharon, Eftychia Markopoulou and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. 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. Article
  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

20 authors.

Jimeen YooCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Gayatri MainkarCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Matteo GhiringhelliCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Bernardo Gindri Dos SantosCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Magdalena M ŻakCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Keerat KaurCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ann Anu KurianCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Matthew AdjmiCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Segev SharonCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Eftychia MarkopoulouCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Lucia ŽigováCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Daniela HirschCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Sydney PessinCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Rachel HananCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Juan Luis Escano AbreuCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Niki BrisnovaliCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Nicole DuboisCell, Development/Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Leigh GoedekeCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mengcheng ShenDepartment of Medicine, Division of Cardiology, Center for Cardiovascular Research, Washington University, Saint Louis, Missouri, USA.
Lior ZangiCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID https://orcid.org/0000-0002-6153-9857

Funding

Icahn School of Medicine at Mount Sinai and NIH R01 HL142768-0Icahn School of Medicine at Mount Sinai and NIH R01 HL149137-01
6 · The paper itself

Abstract

Doxorubicin (Dox) is a widely employed chemotherapeutic agent, but its use is clinically limited by dose-accumulative cardiotoxicity. More specifically, Dox induces oxidative stress and causes pro-apoptotic ceramide accumulation in cardiomyocytes (CMs). Acid ceramidase (AC) modified mRNA (modRNA) has been shown to reduce ceramide levels and protect the heart following ischemic injury; however, therapeutic modRNA applications have been hindered by the need for invasive delivery. Here, we present a platform for minimally intrusive transmission of modRNA to the heart. This CM-selective modRNA translational system (cmSMRTs) is encapsulated in lipid nanoparticles for intravenous (IV) delivery to enable systemic administration with high cardiac selectivity via microRNA-guided translational control (miR143 and miR122) to suppress off-target expression in other tissues, including tumors. In vitro, AC treatment preserved sarcomere structure, calcium handling, and mitochondrial function in Dox-treated human induced pluripotent stem cell (iPSC)-derived CMs. Moreover, weekly IV delivery of this modRNA prevented cardiac dysfunction, fibrosis, and atrophy in chronic Dox-induced cardiotoxicity models. Notably, this cardioprotection is achieved without either compromising Dox's anti-tumor efficacy or producing overall toxicity. These findings establish cmSMRTs 143-122 as a minimally invasive, cardiac-selective mRNA therapy platform with strong potential to prevent chemotherapy-induced cardiotoxicity.

Indexed as

Antineoplastic AgentsCardiotoxicityDoxorubicinMyocytes, CardiacRNA, MessengerAnimalsHumansInduced Pluripotent Stem CellsMiceAntineoplastic AgentsDoxorubicinRNA, Messengercardiac‐selective deliveryDox cardiotoxicitymodified mRNA

Identifiers

PMID41545029
PMCPMC12915083

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.