Evidence map›Paper›PMID 40808258›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Optimized chemical structure extends silencing duration of therapeutic siRNAs in dividing cancer and immune cells.

Anastasia Kremer, Tatyana Ryaykenen, Xavier Segarra-Visent, Melanie Sauer, Leon Breuer, Yiying Wu, Qi Tang, David A Cooper, Dimas Echeverria, Clothilde Philouze and 3 more

Abstract read
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In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 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

13 authors.

Anastasia KremerDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
Tatyana RyaykenenDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
Xavier Segarra-VisentDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
Melanie SauerDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
Leon BreuerDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
Yiying WuDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
Qi TangRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA; Department of Dermatology, University of Massachusetts Chan Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
David A CooperRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Dimas EcheverriaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Clothilde PhilouzeTransCure Bioservices, 260 Av. Marie Curie, 74160 Archamps, France.
Emilie BayonTransCure Bioservices, 260 Av. Marie Curie, 74160 Archamps, France.
Dan GeorgessTransCure Bioservices, 260 Av. Marie Curie, 74160 Archamps, France.
Reka A HarasztiDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany; Gene and RNA Therapy Center (GRTC), Faculty of Medicine, University Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany. Electronic address: reka.haraszti@med.uni-tuebingen.de.

Funding

High-throughput Oligonucleotide Production SystemS10OD036329 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2024 to 2024
$1.4M
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
NIH HHS S10 OD020012NIH HHS S10 OD036329
6 · The paper itself

Abstract

RNA interference (RNAi)-based medicines offer precise targeting of virtually any transcript, making them an appealing new drug class for immuno-oncology. While RNAi therapies are highly effective in non-dividing cells, their efficacy in rapidly dividing cells, crucial for immuno-oncology, remains largely unexplored. Previous data suggest that full chemical modification of short interfering RNAs (siRNAs) in dividing cells has not consistently extended silencing duration, unlike in non-dividing cells. The present study explores key factors influencing the duration of effect of RNAi-based therapeutics (siRNAs) in dividing cancer and immune cells. Saturation of intracellular depots, a strategy to prolong silencing duration in non-dividing hepatocytes, had minimal impact on siRNA effect duration in dividing cells. However, modifying the guide strand with a 5'-(E)-vinylphosphonate significantly extended siRNA silencing duration to over 30 days both in vitro and in vivo. Our findings enable the rational design of the chemical architecture and administration regimens of RNAi-based therapies in immuno-oncology.

Indexed as

Cell DivisionNeoplasmsRNA InterferenceRNA, Small InterferingAnimalsCell Line, TumorHepatocytesHumansMiceT-LymphocytesRNA, Small Interfering5′-(E)-vinylphosphonateimmuno-oncologyrapidly dividing cellssilencing durationsiRNA

Identifiers

PMID40808258
PMCPMC12614277

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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.