Evidence map›Paper›PMID 35569584›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2022

Hydroxycholesterol substitution in ionizable lipid nanoparticles for mRNA delivery to T cells.

Savan K Patel, Margaret M Billingsley, Caitlin Frazee, Xuexiang Han, Kelsey L Swingle, Jingya Qin, Mohamad-Gabriel Alameh, Karin Wang, Drew Weissman, Michael J Mitchell

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
9.3field-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

64 citing papers in PubMed, 112 citations in OpenAlex.

  1. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
    Review
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  4. Article
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  6. Article
  7. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  8. Review
  9. Article
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  12. Article
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  14. Article
  15. Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases.Molecular therapy. Methods & clinical development · 2025
    Review
  18. Review
  19. Review
  20. [Research progress on lipid nanoparticle messenger RNA delivery system].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Review

4 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 3 institutions in 1 country.

Savan K PatelDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Margaret M BillingsleyDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Caitlin FrazeeDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Xuexiang HanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kelsey L SwingleDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jingya QinDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mohamad-Gabriel AlamehPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Karin WangDepartment of Bioengineering, Temple University, Philadelphia, PA 19122, USA.
Drew WeissmanPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, 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.
University of Pennsylvania · USCalifornia Institute for Regenerative Medicine · USTemple University · US

Funding

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
Ionizable lipid nanoparticles for the delivery of mRNA for CAR T cell engineeringF31CA260922 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BILLINGSLEY, MARGARET M. · 2021 to 2022
$77k
NCATS NIH HHS DP2 TR002776NCI NIH HHS F31 CA260922NCI NIH HHS R01 CA241661NCI NIH HHS R37 CA244911NIDDK NIH HHS R01 DK123049
6 · The paper itself

Abstract

Delivery of nucleic acids, such as mRNA, to immune cells has become a major focus in the past decade with ionizable lipid nanoparticles (LNPs) emerging as a clinically-validated delivery platform. LNPs-typically composed of ionizable lipids, cholesterol, phospholipids, and polyethylene glycol lipids -have been designed and optimized for a variety of applications including cancer therapies, vaccines, and gene editing. However, LNPs have only recently been investigated for delivery to T cells, which has various therapeutic applications including the engineering of T cell immunotherapies. While several LNP formulations have been evaluated for mRNA delivery, recent work has demonstrated that the utilization of cholesterol analogs may enhance mRNA delivery. Other studies have shown that cholesterols modified with hydroxyl groups can alter endocytic recycling mechanisms. Here, we engineered a library of LNPs incorporating hydroxycholesterols to evaluate their impact on mRNA delivery to T cells by leveraging endosomal trafficking mechanisms. Substitution of 25% and 50% 7α-hydroxycholesterol for cholesterol in LNPs enhanced mRNA delivery to primary human T cells ex vivo by 1.8-fold and 2.0-fold, respectively. Investigation of endosomal trafficking revealed that these modifications also increase late endosome production and reduce the presence of recycling endosomes. These results suggest that hydroxyl modification of cholesterol molecules incorporated into LNP formulations provides a mechanism for improving delivery of nucleic acid cargo to T cells for a range of immunotherapy applications.

Indexed as

LipidsNanoparticlesCholesterolHumansHydroxycholesterolsLiposomesRNA, MessengerT-LymphocytesCholesterolHydroxycholesterolsLipid NanoparticlesLipidsLiposomesRNA, MessengerCholesterolEndosomal traffickingLipid nanoparticlesmRNA delivery

Identifiers

PMID35569584
PMCPMC9376797
OpenAlexW4280635747

What OpenQuestion holds

Textmetadata
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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 OpenQuestion graph.