Evidence map›Paper›PMID 31678653›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2019

Ionizable lipid nanoparticles encapsulating barcoded mRNA for accelerated in vivo delivery screening.

Pedro P G Guimaraes, Rui Zhang, Roman Spektor, Mingchee Tan, Amanda Chung, Margaret M Billingsley, Rakan El-Mayta, Rachel S Riley, Lili Wang, James M Wilson and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 1 pooled it
5.9field-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

108 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.

  1. Pooled it
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  7. Single-ligand dual-targeting lipid nanoparticles for therapeutic mRNA delivery to glioblastoma across the blood-brain barrier.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
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  20. High-Throughput Strategies for Streamlining Lipid Nanoparticle Development Pipeline.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review

48 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 4 institutions in 2 countries.

Pedro P G GuimaraesDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States; Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Rui ZhangDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Roman SpektorGraduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, NY, United States.
Mingchee TanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Amanda ChungDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Margaret M BillingsleyDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Rakan El-MaytaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Rachel S RileyDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Lili WangGene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
James M WilsonGene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: mjmitch@seas.upenn.edu.
University of Pennsylvania · USCalifornia Institute for Regenerative Medicine · USCornell University · USUniversidade Federal de Minas Gerais · BR

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
A data-driven drug delivery (4D) platform for probing and treating the chemoresistant bone marrow microenvironmentDP2TR002776 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, MICHAEL J · 2018 to 2018
$2.4M
NCATS NIH HHS DP2 TR002776NCI NIH HHS P30 CA016520NHLBI NIH HHS T32 HL007954
6 · The paper itself

Abstract

Messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapy, with the potential to induce protein production to treat and prevent a range of diseases. However, the widespread use of mRNA as a therapeutic requires safe and effective in vivo delivery technologies. Libraries of ionizable lipid nanoparticles (LNPs) have been designed to encapsulate mRNA, prevent its degradation, and mediate intracellular delivery. However, these LNPs are typically characterized and screened in an in vitro setting, which may not fully replicate the biological barriers that they encounter in vivo. Here, we designed and evaluated a library of engineered LNPs containing barcoded mRNA (b-mRNA) to accelerate the screening of mRNA delivery platforms in vivo. These b-mRNA are similar in structure and function to regular mRNA, and contain barcodes that enable their delivery to be quantified via deep sequencing. Using a mini-library of b-mRNA LNPs formulated via microfluidic mixing, we show that these different formulations can be pooled together, administered intravenously into mice as a single pool, and their delivery to multiple organs (liver, spleen, brain, lung, heart, kidney, pancreas, and muscle) can be quantified simultaneously using deep sequencing. In the context of liver and spleen delivery, LNPs that exhibited high b-mRNA delivery also yielded high luciferase expression, indicating that this platform can identify lead LNP candidates as well as optimal formulation parameters for in vivo mRNA delivery. Interestingly, LNPs with identical formulation parameters that encapsulated different types of nucleic acid barcodes (b-mRNA versus a DNA barcode) altered in vivo delivery, suggesting that the structure of the barcoded nucleic acid affects LNP in vivo delivery. This platform, which enables direct barcoding and subsequent quantification of a functional mRNA, can accelerate the in vivo screening and design of LNPs for mRNA therapeutic applications such as CRISPR-Cas9 gene editing, mRNA vaccination, and other mRNA-based regenerative medicine and protein replacement therapies.

Indexed as

Gene Transfer TechniquesNanoparticlesAnimalsElectronic Data ProcessingFemaleGenetic TherapyLipidsMiceMice, Inbred C57BLMicrofluidicsRNA, MessengerLipidsRNA, MessengerGene deliveryGene therapyHigh-throughput screeningmRNANanoparticle

Identifiers

PMID31678653
PMCPMC7032071
OpenAlexW2987798976

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.