Evidence map›Paper›PMID 38871178›Full record

ArticleMolecular metabolism2024

Lipid-encapsulated mRNA encoding an extended serum half-life interleukin-22 ameliorates metabolic disease in mice.

Susanna Canali, Alexander W Fischer, Mychael Nguyen, Karl Anderson, Lorna Wu, Anne-Renee Graham, Chiaowen Joyce Hsiao, Chinmayi Bankar, Nancy Dussault, Veronica Ritchie and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2024. 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. 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

18 authors.

Susanna CanaliModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Susanna.Canali@modernatx.com.
Alexander W FischerModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: alexanderfischer212@gmail.com.
Mychael NguyenModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: mychaelnguyen@gmail.com.
Karl AndersonModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Karl.Anderson@modernatx.com.
Lorna WuModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: lwu2@wellesley.edu.
Anne-Renee GrahamModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Anne-Renee.Graham@modernatx.com.
Chiaowen Joyce HsiaoModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: chiaowen.hsiao@modernatx.com.
Chinmayi BankarModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Chinmayi.Bankar@modernatx.com.
Nancy DussaultModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Nancy.Dussault@modernatx.com.
Veronica RitchieModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Veronica.Ritchie@modernatx.com.
Meagan GoodridgeModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: meaganlgoodridge@gmail.com.
Todd SparrowModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Todd.Sparrow@modernatx.com.
Allison PannoniModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: allisonpannoni@gmail.com.
Sze-Wah TseModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Eva.Tse@modernatx.com.
Vivienne WooModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Vivienne.Woo@modernatx.com.
Kaitlin KlovdahlModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Kaitlin.Klovdahl@modernatx.com.
Jared IacovelliModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: jared.iacovelli@gmail.com.
Eric HuangModerna, Inc., 325 Binney Street, Cambridge, MA 02142, USA. Electronic address: Eyhuang01@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveInterleukin (IL)-22 is a potential therapeutic protein for the treatment of metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease due to its involvement in multiple cellular pathways and observed hepatoprotective effects. The short serum half-life of IL-22 has previously limited its use in clinical applications; however, the development of mRNA-lipid nanoparticle (LNP) technology offers a novel therapeutic approach that uses a host-generated IL-22 fusion protein. In the present study, the effects of administration of an mRNA-LNP encoding IL-22 on metabolic disease parameters was investigated in various mouse models.

methodsC57BL/6NCrl mice were used to confirm mouse serum albumin (MSA)-IL-22 protein expression prior to assessments in C57BL/6NTac and CETP/ApoB transgenic mouse models of metabolic disease. Mice were fed either regular chow or a modified amylin liver nonalcoholic steatohepatitis-inducing diet prior to receiving either LNP-encapsulated MSA-IL-22 or MSA mRNA via intravenous or intramuscular injection. Metabolic markers were monitored for the duration of the experiments, and postmortem histology assessment and analysis of metabolic gene expression pathways were performed.

resultsMSA-IL-22 was detectable for ≥8 days following administration. Improvements in body weight, lipid metabolism, glucose metabolism, and lipogenic and fibrotic marker gene expression in the liver were observed in the MSA-IL-22-treated mice, and these effects were shown to be durable.

conclusionsThese results support the application of mRNA-encoded IL-22 as a promising treatment strategy for metabolic syndrome and associated comorbidities in human populations.

Indexed as

Interleukin-22InterleukinsMetabolic DiseasesMice, Inbred C57BLRNA, MessengerAnimalsDisease Models, AnimalHalf-LifeLipidsLiposomesLiverMaleMiceMice, TransgenicNanoparticlesNon-alcoholic Fatty Liver DiseaseInterleukin-22InterleukinsLipid NanoparticlesLipidsLiposomesRNA, Messengerinterleukin-22Lipid nanoparticle therapeuticMessenger RNAMetabolic disordersMetabolic dysfunction-associated steatotic liver diseaseSerum lipid parameters

Identifiers

PMID38871178
PMCPMC11296054

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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.