Evidence map›Paper›PMID 38583366›Full record

ArticleBiomaterials2024

Optimization of lipid nanoparticles for gene editing of the liver via intraduodenal delivery.

Yining Zhu, Shuting Sarah Cai, Jingyao Ma, Leonardo Cheng, Christine Wei, Ataes Aggarwal, Wu Han Toh, Charles Shin, Ruochen Shen, Jiayuan Kong and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. NNature · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Garcinone C inhibits pseudorabies virus replication through EGF/PI3K/Akt axis.Frontiers in cellular and infection microbiology · 2025
    Article
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

14 authors at 3 institutions in 1 country.

Yining ZhuDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
Shuting Sarah CaiDepartment of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Jingyao MaInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Leonardo ChengDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
Christine WeiDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
Ataes AggarwalDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD, 21218, USA.
Wu Han TohInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
Charles ShinDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA.
Ruochen ShenDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
Jiayuan KongInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Shuming Alan MaoDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD, 21218, USA.
Yeh-Hsing LaoDepartment of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Kam W LeongDepartment of Biomedical Engineering, Columbia University, New York, NY, 10027, USA; Department of Systems Biology, Columbia University Medical Center, New York, NY, 10032, USA. Electronic address: kam.leong@columbia.edu.
Hai-Quan MaoDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA. Electronic address: hmao@jhu.edu.
Johns Hopkins University · USColumbia University · USColumbia University Irving Medical Center · US

Funding

BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
Development of an oral liver-targeted prime-and-trap malaria vaccineU01AI155313 · NIAID · UNIVERSITY OF WASHINGTON · PI MURPHY, SEAN C · 2021 to 2025
$4.1M
Integrated Microphysiological System of Cerebral Organoid and Blood Vessel for Disease Modeling and Neuropsychiatric Drug screeningUH3TR002151 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LEONG, KAM W · 2020 to 2022
$3.6M
NCATS NIH HHS UH3 TR002151NIAID NIH HHS U01 AI155313NIGMS NIH HHS T32 GM007057
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) have recently emerged as successful gene delivery platforms for a diverse array of disease treatments. Efforts to optimize their design for common administration methods such as intravenous injection, intramuscular injection, or inhalation, revolve primarily around the addition of targeting ligands or the choice of ionizable lipid. Here, we employed a multi-step screening method to optimize the type of helper lipid and component ratios in a plasmid DNA (pDNA) LNP library to efficiently deliver pDNA through intraduodenal delivery as an indicative route for oral administration. By addressing different physiological barriers in a stepwise manner, we down-selected effective LNP candidates from a library of over 1000 formulations. Beyond reporter protein expression, we assessed the efficiency in non-viral gene editing in mouse liver mediated by LNPs to knockdown PCSK9 and ANGPTL3 expression, thereby lowering low-density lipoprotein (LDL) cholesterol levels. Utilizing an all-in-one pDNA construct with Strep. pyogenes Cas9 and gRNAs, our results showcased that intraduodenal administration of selected LNPs facilitated targeted gene knockdown in the liver, resulting in a 27% reduction in the serum LDL cholesterol level. This LNP-based all-in-one pDNA-mediated gene editing strategy highlights its potential as an oral therapeutic approach for hypercholesterolemia, opening up new possibilities for DNA-based gene medicine applications.

Indexed as

Gene EditingLipidsLiverNanoparticlesAnimalsDNADuodenumGene Transfer TechniquesHumansMiceMice, Inbred C57BLPlasmidsProprotein Convertase 9DNALipidsProprotein Convertase 9HypercholesterolemiaIntraduodenal injectionLipid nanoparticlesLiver gene editingOral deliveryPlasmid DNA

Identifiers

PMID38583366
PMCPMC11099935
OpenAlexW4393928728

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.