Evidence map›Paper›PMID 23306021›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2013

Transfection efficiency and transgene expression kinetics of mRNA delivered in naked and nanoparticle format.

Kyle K L Phua, Kam W Leong, Smita K Nair

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 1 pooled it
–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

91 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Developing Biomaterial-Based mRNA Delivery System for Lung Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  4. Lipid nanoparticles: Composition, formulation, and application.Molecular therapy. Methods & clinical development · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Delivery of mRNA with Histidine-Lysine Peptides.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  15. Review
  16. Article
  17. The mixing method used to formulate lipid nanoparticles affects mRNA delivery efficacy and organ tropism.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2023
    Article
  18. Delivery of gene editing therapeutics.Nanomedicine : nanotechnology, biology, and medicine · 2023
    Review
  19. Review
  20. Article

31 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

3 authors.

Kyle K L PhuaDepartment of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Kam W Leong
Smita K Nair

Funding

Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Overcoming Immunosenescence by Nanoparticle-Mediated ActivationR01AI096305 · NIAID · DUKE UNIVERSITY · PI ABRAHAM, SOMAN N, LEONG, KAM W · 2012 to 2016
$1.8M
Derivation of Functional Neurons from Human Adult Cells by Nonviral Gene DeliveryR21EB015300 · NIBIB · DUKE UNIVERSITY · PI LEONG, KAM W · 2012 to 2013
$421k
NHLBI NIH HHS R01 HL109442NIAID NIH HHS AI096305NIAID NIH HHS R01 AI096305NIBIB NIH HHS R21 EB015300
6 · The paper itself

Abstract

Transfection efficiencies and transgene expression kinetics of messenger RNA (mRNA), an emerging class of nucleic acid-based therapeutics, have been poorly characterized. In this study, we evaluated transfection efficiencies of mRNA delivered in naked and nanoparticle format in vitro and in vivo using GFP and luciferase as reporters. While mRNA nanoparticles transfect primary human and mouse dendritic cells (DCs) efficiently in vitro, naked mRNA could not produce any detectable gene product. The protein expression of nanoparticle-mediated transfection in vitro peaks rapidly within 5-7h and decays in a biphasic manner. In vivo, naked mRNA is more efficient than mRNA nanoparticles when administered subcutaneously. In contrast, mRNA nanoparticle performs better when administered intranasally and intravenously. Gene expression is most transient when delivered intravenously in nanoparticle format with an apparent half-life of 1.4h and lasts less than 24h, and most sustained when delivered in the naked format subcutaneously at the base of tail with an apparent half-life of 18h and persists for at least 6days. Notably, exponential decreases in protein expression are consistently observed post-delivery of mRNA in vivo regardless of the mode of delivery (naked or nanoparticle) or the site of administration. This study elucidates the performance of mRNA transfection and suggests a niche for mRNA therapeutics when predictable in vivo transgene expression kinetics is imperative.

Indexed as

Gene ExpressionAdministration, IntranasalAnimalsCells, CulturedDendritic CellsDrug CarriersHumansInjections, IntravenousInjections, SubcutaneousKineticsLuciferasesMiceMice, Inbred BALB CMice, Inbred C57BLNanoparticlesPrimary Cell CultureDrug CarriersLuciferasesRNA, Messenger

Identifiers

PMID23306021
PMCPMC3594075

What OpenQuestion holds

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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.