Evidence map›Paper›PMID 39293650›Full record

ReviewAdvanced drug delivery reviews2024

Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome.

Kaitlin Mrksich, Marshall S Padilla, Michael J Mitchell

Abstract readReview
In one paragraph

Review in Advanced drug delivery reviews, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
–field-weighted citation impact
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

57 citing papers in PubMed.

  1. Overview of Delivery Methods for Gene Editing.Methods in molecular biology (Clifton, N.J.) · 2027
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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

3 authors.

Kaitlin MrksichDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Marshall S PadillaDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael J MitchellDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: mjmitch@seas.upenn.edu.

Funding

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
Advanced Training at the Interface of Engineering and Oral-Craniofacial SciencesT90DE030854 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI Hyun Koo, Kathleen J Stebe · 2021 to 2026
$1.4M
mRNA lipid nanoparticles for pre-eclampsiaR01HD115877 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael J Mitchell · 2024 to 2026
$1.0M
NCATS NIH HHS DP2 TR002776NICHD NIH HHS R01 HD115877NIDCR NIH HHS T90 DE030854
6 · The paper itself

Abstract

In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the endo-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically overcome endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure-function relationships, with a focus on how they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.

Indexed as

CationsEndosomesLipidsNanoparticlesAnimalsCOVID-19Drug Delivery SystemsHumansLiposomesCationsLipid NanoparticlesLipidsLiposomesEndosomeLipidNanomedicineNanoparticleRNA

Identifiers

PMID39293650
PMCPMC11900896

What Socratic holds

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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 Socratic graph.