Evidence map›Paper›PMID 38648653›Full record

ArticleAdvanced healthcare materials2025

Covalent Polymer-RNA Conjugates for Potent Activation of the RIG-I Pathway.

Christian R Palmer, Lucinda E Pastora, Blaise R Kimmel, Hayden M Pagendarm, Alexander J Kwiatkowski, Payton T Stone, Karan Arora, Nora Francini, Olga Fedorova, Anna M Pyle and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Advanced healthcare materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. 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

11 authors at 2 institutions in 1 country.

Christian R PalmerDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0002-4184-0095
Lucinda E PastoraDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
Blaise R KimmelDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0002-9582-9887
Hayden M PagendarmDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0001-7611-6120
Alexander J KwiatkowskiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0001-5435-3555
Payton T StoneDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0002-8105-0610
Karan AroraDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0003-1472-1637
Nora FranciniDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0001-7681-6442
Olga FedorovaDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06511, USA.
Anna M PyleDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06511, USA.ORCID 0000-0001-9045-8872
John T WilsonDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.ORCID 0000-0002-9144-2634
Vanderbilt University · USHoward Hughes Medical Institute · US

Funding

MULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4M
Chemistry-Biology Interface Training GrantT32GM065086 · NIGMS · VANDERBILT UNIVERSITY · PI BACHMANN, BRIAN O, SULIKOWSKI, GARY ALLEN · 2002 to 2022
$7.0M
Integrated Training in Engineering and DiabetesT32DK101003 · NIDDK · VANDERBILT UNIVERSITY · PI Jamey D. Young · 2014 to 2026
$3.9M
RIG-I Activating Nanoparticles for ImmunopotentiationR01EB033822 · NIBIB · VANDERBILT UNIVERSITY · PI Anna Marie Pyle, John Tanner Wilson · 2022 to 2026
$2.4M
Congressionally Directed Medical Research Programs W81XWH-20-1-0624National Science Foundation CBET-1554623National Science Foundation Graduate Research Fellowship Program 1937963NCI NIH HHS T32 CA009592NCI NIH HHS T32CA009592NIBIB NIH HHS R01 EB033822NIBIB NIH HHS R01EB033822NIDDK NIH HHS T32 DK101003NIDDK NIH HHS T32DK101003NIGMS NIH HHS T32 GM065086NIGMS NIH HHS T32GM065086Pharmaceutical Research and Manufacturers of America Foundation Postdoctoral Fellowship In Drug DeliveryVanderbilt-Ingram Cancer Center Ambassador Discovery GrantVanderbilt University School of Engineering
6 · The paper itself

Abstract

RNA ligands of retinoic acid-inducible gene I (RIG-I) are a promising class of oligonucleotide therapeutics with broad potential as antiviral agents, vaccine adjuvants, and cancer immunotherapies. However, their translation has been limited by major drug delivery barriers, including poor cellular uptake, nuclease degradation, and an inability to access the cytosol where RIG-I is localized. Here this challenge is addressed by engineering nanoparticles that harness covalent conjugation of 5'-triphospate RNA (3pRNA) to endosome-destabilizing polymers. Compared to 3pRNA loaded into analogous nanoparticles via electrostatic interactions, it is found that covalent conjugation of 3pRNA improves loading efficiency, enhances immunostimulatory activity, protects against nuclease degradation, and improves serum stability. Additionally, it is found that 3pRNA could be conjugated via either a disulfide or thioether linkage, but that the latter is only permissible if conjugated distal to the 5'-triphosphate group. Finally, administration of 3pRNA-polymer conjugates to mice significantly increases type-I interferon levels relative to analogous carriers that use electrostatic 3pRNA loading. Collectively, these studies have yielded a next-generation polymeric carrier for in vivo delivery of 3pRNA, while also elucidating new chemical design principles for covalent conjugation of 3pRNA with potential to inform the further development of therapeutics and delivery technologies for pharmacological activation of RIG-I.

Indexed as

DEAD Box Protein 58PolymersRNAAnimalsHumansMiceNanoparticlesReceptors, ImmunologicDEAD Box Protein 58PolymersReceptors, ImmunologicRIGI protein, humanRNAbioconjugationinnate immunitynanoparticlenucleic acid therapeuticoligonucleotidepolymerRIG‐I

Identifiers

PMID38648653
PMCPMC11493851
OpenAlexW4395013325

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.