Evidence map›Paper›PMID 32937431›Full record

ArticleScience advances2020

Single-dose mRNA therapy via biomaterial-mediated sequestration of overexpressed proteins.

Andrew S Khalil, Xiaohua Yu, Jennifer M Umhoefer, Connie S Chamberlain, Linzie A Wildenauer, Gaoussou M Diarra, Timothy A Hacker, William L Murphy

Abstract read
In one paragraph

Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. Review
  3. Unlock the sustained therapeutic efficacy of mRNA.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. mRNA vaccines in disease prevention and treatment.Signal transduction and targeted therapy · 2023
    Review
  8. Matrices Activated with Messenger RNA.Journal of functional biomaterials · 2023
    Review
  9. Article
  10. Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.Journal of tissue engineering and regenerative medicine · 2022
    Review
  11. Article
  12. Gene therapy to enhance angiogenesis in chronic wounds.Molecular therapy. Nucleic acids · 2022
    Review
  13. Article
  14. Review
  15. The infinite possibilities of RNA therapeutics.Journal of industrial microbiology & biotechnology · 2021
    Article
  16. Review
  17. Review
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.

Andrew S KhalilDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.ORCID 0000-0003-1526-6656
Xiaohua YuDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.
Jennifer M UmhoeferDepartment of Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.ORCID 0000-0002-8563-9641
Connie S ChamberlainDepartment of Orthopedics and Rehabilitation, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.ORCID 0000-0002-4980-4347
Linzie A WildenauerDepartment of Orthopedics and Rehabilitation, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.ORCID 0000-0002-8843-7973
Gaoussou M DiarraCardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.
Timothy A HackerCardiovascular Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.
William L MurphyDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA. wlmurphy@wisc.edu.ORCID 0000-0001-5577-7739

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
Modulation of the Immune System to Improve Ligament/Ligament Graft HealingR01AR059916 · NIAMS · UNIVERSITY OF WISCONSIN-MADISON · PI MURPHY, WILLIAM L., VANDERBY, RAY · 2010 to 2014
$1.4M
Matrices for optimal endogenous progenitor cell recruitment and functionR21EB019558 · NIBIB · UNIVERSITY OF WISCONSIN-MADISON · PI MURPHY, WILLIAM L. · 2016 to 2017
$409k
NIAMS NIH HHS R01 AR059916NIBIB NIH HHS R21 EB019558NIGMS NIH HHS T32 GM008349
6 · The paper itself

Abstract

Nonviral mRNA delivery is an attractive therapeutic gene delivery strategy, as it achieves efficient protein overexpression in vivo and has a desirable safety profile. However, mRNA's short cytoplasmic half-life limits its utility to therapeutic applications amenable to repeated dosing or short-term overexpression. Here, we describe a biomaterial that enables a durable in vivo response to a single mRNA dose via an "overexpress and sequester" mechanism, whereby mRNA-transfected cells locally overexpress a growth factor that is then sequestered within the biomaterial to sustain the biologic response over time. In a murine diabetic wound model, this strategy demonstrated improved wound healing compared to delivery of a single mRNA dose alone or recombinant protein. In addition, codelivery of anti-inflammatory proteins using this biomaterial eliminated the need for mRNA chemical modification for in vivo therapeutic efficacy. The results support an approach that may be broadly applicable for single-dose delivery of mRNA without chemical modification.

Indexed as

Biocompatible MaterialsWound HealingAnimalsGene Transfer TechniquesIntercellular Signaling Peptides and ProteinsMiceRNA, MessengerBiocompatible MaterialsIntercellular Signaling Peptides and ProteinsRNA, Messenger

Identifiers

PMID32937431
PMCPMC7458450

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.