Evidence map›Paper›PMID 28836442›Full record

ArticleNano letters2017

Boosting Intracellular Delivery of Lipid Nanoparticle-Encapsulated mRNA.

Siddharth Patel, N Ashwanikumar, Emily Robinson, Allison DuRoss, Conroy Sun, Kerry E Murphy-Benenato, Cosmin Mihai, Örn Almarsson, Gaurav Sahay

Abstract read
In one paragraph

Article in Nano letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

135 citing papers in PubMed, 233 citations in OpenAlex.

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  12. Nanocarrier-mediated CRISPR-Cas delivery: a novel approach against antibiotic-resistant superbugs.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Review
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  17. Rational design of lipid nanoparticles for enabling gene therapies.Molecular therapy. Methods & clinical development · 2025
    Review
  18. Review
  19. Review
  20. Cubic Phase-Inducible Zwitterionic Phospholipids Improve the Functional Delivery of mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article

75 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.

Siddharth PatelDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, Oregon 97201, United States.
N AshwanikumarDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, Oregon 97201, United States.
Emily RobinsonDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, Oregon 97201, United States.
Allison DuRossDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, Oregon 97201, United States.
Conroy SunDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, Oregon 97201, United States.
Kerry E Murphy-BenenatoModerna Therapeutics , 200 Technology Square, Cambridge, Massachusetts 02139, United States.
Cosmin MihaiModerna Therapeutics , 200 Technology Square, Cambridge, Massachusetts 02139, United States.
Örn AlmarssonModerna Therapeutics , 200 Technology Square, Cambridge, Massachusetts 02139, United States.
Gaurav SahayDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, Oregon 97201, United States.ORCID 0000-0003-1071-0500
Oregon State University · USModerna Therapeutics (United States) · US

Funding

Synergistic combination of nanotechnology and radiation in medicineR35GM119839 · NIGMS · OREGON STATE UNIVERSITY · PI SUN, CONROY GHIN CHEE · 2016 to 2020
$1.8M
Mechanisms of Intracellular trafficking and endosomal escape of nanoparticles for mRNA deliveryR15EB021581 · NIBIB · OREGON STATE UNIVERSITY · PI SAHAY, GAURAV · 2017 to 2017
$441k
NIBIB NIH HHS R15 EB021581NIGMS NIH HHS R35 GM119839
6 · The paper itself

Abstract

Intracellular delivery of mRNA holds great potential for vaccine1-3 and therapeutic4 discovery and development. Despite increasing recognition of the utility of lipid-based nanoparticles (LNPs) for intracellular delivery of mRNA, particle engineering is hindered by insufficient understanding of endosomal escape, which is believed to be a main limiter of cytosolic availability and activity of the nucleic acid inside the cell. Using a series of CRISPR-based genetic perturbations of the lysosomal pathway, we have identified that late endosome/lysosome (LE/Ly) formation is essential for functional delivery of exogenously presented mRNA. Lysosomes provide a spatiotemporal hub to orchestrate mTOR signaling and are known to control cell proliferation, nutrient sensing, ribosomal biogenesis, and mRNA translation. Through modulation of the mTOR pathway we were able to enhance or inhibit LNP-mediated mRNA delivery. To further boost intracellular delivery of mRNA, we screened 212 bioactive lipid-like molecules that are either enriched in vesicular compartments or modulate cell signaling. Surprisingly, we have discovered that leukotriene-antagonists, clinically approved for treatment of asthma and other lung diseases, enhance intracellular mRNA delivery in vitro (over 3-fold, p < 0.005) and in vivo (over 2-fold, p < 0.005). Understanding LNP-mediated intracellular delivery will inspire the next generation of RNA therapeutics that have high potency and limited toxicity.

Indexed as

Gene Transfer TechniquesAnimalsCell LineEndosomesFemaleHeLa CellsHep G2 CellsHumansLipid MetabolismLipidsLysosomesMice, Inbred BALB CNanoparticlesRNA, MessengerSignal TransductionTOR Serine-Threonine KinasesLipidsRNA, MessengerTOR Serine-Threonine Kinasesbioactive lipidsendosome escapeIntracellular deliverylipid nanoparticlesmRNAmTOR

Identifiers

PMID28836442
PMCPMC5623340
OpenAlexW2748490245

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.