Evidence map›Paper›PMID 34600888›Full record

ArticleThe Journal of biological chemistry2021

Exosome-mediated mRNA delivery in vivo is safe and can be used to induce SARS-CoV-2 immunity.

Shang Jui Tsai, Nadia A Atai, Mafalda Cacciottolo, Justin Nice, Arjang Salehi, Chenxu Guo, Alanna Sedgwick, Saravana Kanagavelu, Stephen J Gould

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
8.8field-weighted citation impact, top 1% 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

96 citing papers in PubMed, 137 citations in OpenAlex.

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36 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Shang Jui TsaiDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nadia A AtaiCapricor Therapeutics, Inc, Beverly Hills, California, USA.
Mafalda CacciottoloCapricor Therapeutics, Inc, Beverly Hills, California, USA.
Justin NiceCapricor Therapeutics, Inc, Beverly Hills, California, USA.
Arjang SalehiCapricor Therapeutics, Inc, Beverly Hills, California, USA.
Chenxu GuoDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alanna SedgwickCapricor Therapeutics, Inc, Beverly Hills, California, USA.
Saravana KanagaveluCapricor Therapeutics, Inc, Beverly Hills, California, USA.
Stephen J GouldDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: sgould@jhmi.edu.
Capricor Therapeutics (United States) · USJohns Hopkins University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Functional delivery of mRNA has high clinical potential. Previous studies established that mRNAs can be delivered to cells in vitro and in vivo via RNA-loaded lipid nanoparticles (LNPs). Here we describe an alternative approach using exosomes, the only biologically normal nanovesicle. In contrast to LNPs, which elicited pronounced cellular toxicity, exosomes had no adverse effects in vitro or in vivo at any dose tested. Moreover, mRNA-loaded exosomes were characterized by efficient mRNA encapsulation (∼90%), high mRNA content, consistent size, and a polydispersity index under 0.2. Using an mRNA encoding the red light-emitting luciferase Antares2, we observed that mRNA-loaded exosomes were superior to mRNA-loaded LNPs at delivering functional mRNA into human cells in vitro. Injection of Antares2 mRNA-loaded exosomes also led to strong light emission following injection into the vitreous fluid of the eye or into the tissue of skeletal muscle in mice. Furthermore, we show that repeated injection of Antares2 mRNA-loaded exosomes drove sustained luciferase expression across six injections spanning at least 10 weeks, without evidence of signal attenuation or adverse injection site responses. Consistent with these findings, we observed that exosomes loaded with mRNAs encoding immunogenic forms of the SARS-CoV-2 Spike and Nucleocapsid proteins induced long-lasting cellular and humoral responses to both. Taken together, these results demonstrate that exosomes can be used to deliver functional mRNA to and into cells in vivo.

Indexed as

Cells, CulturedExosomesGene Transfer TechniquesHEK293 CellsHumansLipidsNanoparticlesRNA, MessengerSARS-CoV-2LipidsRNA, Messengerantibodycationic lipidCOVID19exosomeextracellular vesicleslipofectionmRNAnucleocapsidspikeT-cell

Identifiers

PMID34600888
PMCPMC8483990
OpenAlexW3204913535

What OpenQuestion 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 OpenQuestion graph.