Evidence map›Paper›PMID 27680591›Full record

ArticleBiomaterials2016

Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo.

Kevin J Kauffman, Faryal F Mir, Siddharth Jhunjhunwala, James C Kaczmarek, Juan E Hurtado, Jung H Yang, Matthew J Webber, Piotr S Kowalski, Michael W Heartlein, Frank DeRosa and 1 more

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 2 pooled it
5.7field-weighted citation impact, top 3% 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

125 citing papers in PubMed, 2 syntheses or guidelines pooled it, 186 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  7. Article
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  10. Article
  11. Characterizing the Impact of the Cell Cycle on mRNA Lipid Nanoparticles.Journal of the American Chemical Society · 2026
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Research progress of mRNA vaccines for infectious diseases.European journal of medical research · 2025
    Review
  18. Article
  19. Article
  20. Review

65 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

11 authors at 3 institutions in 1 country.

Kevin J KauffmanDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Faryal F MirDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Siddharth JhunjhunwalaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
James C KaczmarekDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Juan E HurtadoDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jung H YangDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Matthew J WebberDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Piotr S KowalskiDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Michael W HeartleinShire Pharmaceuticals, Lexington, MA 02421, USA.
Frank DeRosaShire Pharmaceuticals, Lexington, MA 02421, USA.
Daniel G AndersonDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dgander@mit.edu.
Massachusetts Institute of Technology · USTakeda (United States) · USHarvard–MIT Division of Health Sciences and Technology · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
NCI NIH HHS P30 CA014051
6 · The paper itself

Abstract

mRNA has broad potential for treating diseases requiring protein expression. However, mRNA can also induce an immune response with associated toxicity. Replacement of uridine bases with pseudouridine has been postulated to modulate both mRNA immunogenicity and potency. Here, we explore the immune response and activity of lipid nanoparticle-formulated unmodified and pseudouridine-modified mRNAs administered systemically in vivo. Pseudouridine modification to mRNA had no significant effect on lipid nanoparticle physical properties, protein expression in vivo, or mRNA immunogenicity compared to unmodified mRNA when delivered systemically with liver-targeting lipid nanoparticles, but reduced in vitro transfection levels. Indicators of a transient, extracellular innate immune response to mRNA were observed, including neutrophilia, myeloid cell activation, and up-regulation of four serum cytokines. This study provides insight into the immune responses to mRNA lipid nanoparticles, and suggests that pseudouridine modifications may be unnecessary for therapeutic application of mRNA in the liver.

Indexed as

AnimalsCytokinesFemaleGene ExpressionGene Transfer TechniquesHeLa CellsHumansImmunity, InnateLipidsLiverMice, Inbred C57BLMyeloid CellsNanoparticlesParticle SizePseudouridineRNA, MessengerCytokinesLipidsPseudouridineRNA, MessengerBase modificationImmmune responseIn vivoLipid nanoparticlemRNAPseudouridine

Identifiers

PMID27680591
PMCPMC5267554
OpenAlexW2521176812

What OpenQuestion holds

Textmetadata
LicenceTDM
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.