Evidence map›Paper›PMID 34189917›Full record

ArticleNano letters2021

Scalable mRNA and siRNA Lipid Nanoparticle Production Using a Parallelized Microfluidic Device.

Sarah J Shepherd, Claude C Warzecha, Sagar Yadavali, Rakan El-Mayta, Mohamad-Gabriel Alameh, Lili Wang, Drew Weissman, James M Wilson, David Issadore, Michael J Mitchell

Open access · greenAbstract read
In one paragraph

Article in Nano letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed
14.7field-weighted citation impact, top 1% 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

128 citing papers in PubMed, 284 citations in OpenAlex.

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  18. Cationic mRNA Lipid Nanoparticles for Ex Vivo NanoCAR-T Cell Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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68 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

10 authors at 2 institutions in 1 country.

Sarah J ShepherdDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Claude C WarzechaGene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Sagar YadavaliDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Rakan El-MaytaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Mohamad-Gabriel AlamehDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0002-5672-6930
Lili WangGene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Drew WeissmanDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
James M WilsonGene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
David IssadoreDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0002-3628-2244
University of Pennsylvania · USCalifornia Institute for Regenerative Medicine · US

Funding

Center for Sub-Cellular GenomicsRM1HG010023 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI EBERWINE, JAMES H, KIM, JUNHYONG · 2018 to 2022
$11.0M
In utero gene editing to cure a metabolic liver diseaseR01DK123049 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI PERANTEAU, WILLIAM H. · 2020 to 2024
$3.7M
Targeting stem-like cells and their niche in pancreatic cancerR37CA244911 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Tuomas Tammela · 2020 to 2026
$3.4M
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
Modular approach for the delivery of antibodies into the cytoplasm of cellsR01CA241661 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TSOURKAS, ANDREW · 2019 to 2023
$1.8M
Nanomagnetic isolation and sensing for mobile HIV-1 self-testingR61AI147406 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ISSADORE, DAVID AARON · 2019 to 2021
$1.4M
Rapid unbiased isolation and in situ RNA analysis of circulating tumor cells using a magnetic micropore-based diagnostic chipR33CA206907 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ISSADORE, DAVID AARON · 2017 to 2019
$1.1M
A nanomagnetic platform technology to characterize traumatic brain injury using brain derived extracellular vesiclesR21MH118170 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI ISSADORE, DAVID AARON · 2018 to 2019
$414k
Spatially-targeted heating of magnetic nanoparticlesR21EB023989 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI ISSADORE, DAVID AARON · 2018 to 2019
$411k
NCATS NIH HHS DP2 TR002776NCI NIH HHS R01 CA241661NCI NIH HHS R33 CA206907NCI NIH HHS R37 CA244911NHGRI NIH HHS RM1 HG010023NIAID NIH HHS R61 AI147406NIBIB NIH HHS R21 EB023989NIDDK NIH HHS R01 DK123049NIMH NIH HHS R21 MH118170
6 · The paper itself

Abstract

A major challenge to advance lipid nanoparticles (LNPs) for RNA therapeutics is the development of formulations that can be produced reliably across the various scales of drug development. Microfluidics can generate LNPs with precisely defined properties, but have been limited by challenges in scaling throughput. To address this challenge, we present a scalable, parallelized microfluidic device (PMD) that incorporates an array of 128 mixing channels that operate simultaneously. The PMD achieves a >100× production rate compared to single microfluidic channels, without sacrificing desirable LNP physical properties and potency typical of microfluidic-generated LNPs. In mice, we show superior delivery of LNPs encapsulating either Factor VII siRNA or luciferase-encoding mRNA generated using a PMD compared to conventional mixing, with a 4-fold increase in hepatic gene silencing and 5-fold increase in luciferase expression, respectively. These results suggest that this PMD can generate scalable and reproducible LNP formulations needed for emerging clinical applications, including RNA therapeutics and vaccines.

Indexed as

Lab-On-A-Chip DevicesNanoparticlesAnimalsLipidsMiceRNA, MessengerRNA, Small InterferingLipidsRNA, MessengerRNA, Small Interferinggene therapylipid nanoparticlesmRNAsiRNA

Identifiers

PMID34189917
PMCPMC10726372
OpenAlexW3174114275

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.