Evidence map›Paper›PMID 31300730›Full record

ArticleGene therapy2019

Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA.

Anna K Blakney, Paul F McKay, Bárbara Ibarzo Yus, Yoann Aldon, Robin J Shattock

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
8.5field-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

120 citing papers in PubMed, 202 citations in OpenAlex.

  1. Article
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  17. Review
  18. The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  19. Article
  20. Article

60 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

5 authors at 1 institution in 1 country.

Anna K BlakneyDepartment of Medicine, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-5812-9689
Paul F McKayDepartment of Medicine, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-5195-6254
Bárbara Ibarzo YusDepartment of Medicine, Imperial College London, London, UK.
Yoann AldonDepartment of Medicine, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-9831-9391
Robin J ShattockDepartment of Medicine, Imperial College London, London, UK. r.shattock@imperial.ac.uk.ORCID http://orcid.org/0000-0002-4936-1718
Imperial College London · GB

Funding

Medical Research Council MC_PC_17162
6 · The paper itself

Abstract

Self-amplifying RNA (saRNA) is a promising biotherapeutic tool that has been used as a vaccine against both infectious diseases and cancer. saRNA has been shown to induce protein expression for up to 60 days and elicit immune responses with lower dosing than messenger RNA (mRNA). Because saRNA is a large (~9500 nt), negatively charged molecule, it requires a delivery vehicle for efficient cellular uptake and degradation protection. Lipid nanoparticles (LNPs) have been widely used for RNA formulations, where the prevailing paradigm is to encapsulate RNA within the particle, including the first FDA-approved small-interfering siRNA therapy. Here, we compared LNP formulations with cationic and ionizable lipids with saRNA either on the interior or exterior of the particle. We show that LNPs formulated with cationic lipids protect saRNA from RNAse degradation, even when it is adsorbed to the surface. Furthermore, cationic LNPs deliver saRNA equivalently to particles formulated with saRNA encapsulated in an ionizable lipid particle, both in vitro and in vivo. Finally, we show that cationic and ionizable LNP formulations induce equivalent antibodies against HIV-1 Env gp140 as a model antigen. These studies establish formulating saRNA on the surface of cationic LNPs as an alternative to the paradigm of encapsulating RNA.

Indexed as

NanoparticlesAnimalsCationsenv Gene Products, Human Immunodeficiency VirusFatty Acids, MonounsaturatedFemaleHEK293 CellsHIV AntibodiesHumansLipidsLuciferases, FireflyMiceMice, Inbred BALB CParticle SizeQuaternary Ammonium CompoundsRibonucleases1,2-dioleoyloxy-3-(trimethylammonium)propaneCationsdimethyldioctadecylammoniumenv Gene Products, Human Immunodeficiency VirusFatty Acids, Monounsaturatedgp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesLipidsLuciferases, FireflyQuaternary Ammonium CompoundsRibonucleasesRNA, Messenger

Identifiers

PMID31300730
PMCPMC6760535
OpenAlexW2961919374

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.