Evidence map›Paper›PMID 34437913›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2021

Genetic in situ engineering of myeloid regulatory cells controls inflammation in autoimmunity.

N N Parayath, S Hao, S B Stephan, A L Koehne, C E Watson, M T Stephan

Open access · hybridAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Delivery of mRNA for regulating functions of immune cells.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Review
  7. 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

6 authors at 2 institutions in 1 country.

N N ParayathClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
S HaoClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
S B StephanClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
A L KoehneTranslational Pathology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
C E WatsonTranslational Pathology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
M T StephanClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington, Seattle 98195, WA, USA. Electronic address: mstephan@fredhutch.org.
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Developing macrophage reprogramming mRNA nanocarriers for initial clinical testingR01CA263524 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STEPHAN, MATTHIAS · 2021 to 2024
$2.7M
Generating rapid antitumor immunity with lymphocyte-reprogramming nanocarriersR01CA207407 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STEPHAN, MATTHIAS · 2017 to 2021
$1.8M
NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA207407NCI NIH HHS R01 CA263524
6 · The paper itself

Abstract

The ability of myeloid regulatory cells (MRCs) to control immune responses and to promote tolerance has prompted enormous interest in exploiting them therapeutically to treat inflammation, autoimmunity, or to improve outcomes in transplantation. While immunomodulatory small-molecule compounds and antibodies have provided relief for some patients, the dosing entails high systemic drug exposures and thus increased risk of off-target adverse effects. More recently, MRC-based cell-therapy products have entered clinical testing for tolerance induction. However, the elaborate and expensive protocols currently required to manufacture engineered MRCs ex vivo put this approach beyond the reach of many patients who might benefit. A solution could be to directly program MRCs in vivo. Here we describe a targeted nanocarrier that delivers in vitro-transcribed mRNA encoding a key anti-inflammatory mediator. We demonstrate in models of systemic lupus erythematosus that infusions of nanoparticles formulated with mRNA encoding glucocorticoid-induced leucine zipper (GILZ) effectively control the disease. We further establish that these nanoreagents are safe for repeated dosing. Implemented in the clinic, this new therapy could enable physicians to treat autoimmune disease while avoiding systemic treatments that disrupt immune homeostasis.

Indexed as

AutoimmunityLupus Erythematosus, SystemicHumansInflammationMyeloid CellsTranscription FactorsTranscription FactorsAutoimmune diseaseGlucocorticoid-induced leucine zipperIn situ gene therapymRNA

Identifiers

PMID34437913
PMCPMC8599636
OpenAlexW3193478854

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.