Evidence map›Paper›PMID 36634709›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2023

Targeted GATA3 knockdown in activated T cells via pulmonary siRNA delivery as novel therapy for allergic asthma.

Rima Kandil, Domizia Baldassi, Sebastian Böhlen, Joschka T Müller, David C Jürgens, Tonia Bargmann, Susann Dehmel, Yuran Xie, Aditi Mehta, Katherina Sewald and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  9. Nanotechnology-Based Therapeutics for Airway Inflammatory Diseases.Clinical reviews in allergy & immunology · 2025
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  14. Tailoring lipid nanoparticles for T-cell targeting in allergic asthma: Insights into efficacy and specificity.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2024
    Article
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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

11 authors at 4 institutions in 2 countries.

Rima KandilDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University of Munich, Butenandtstraße 5, 81377 Munich, Germany.
Domizia BaldassiDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University of Munich, Butenandtstraße 5, 81377 Munich, Germany.
Sebastian BöhlenFraunhofer Institute of Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) of the German Center for Lung Research (DZL), Hannover, Germany.
Joschka T MüllerDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University of Munich, Butenandtstraße 5, 81377 Munich, Germany.
David C JürgensDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University of Munich, Butenandtstraße 5, 81377 Munich, Germany.
Tonia BargmannFraunhofer Institute of Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) of the German Center for Lung Research (DZL), Hannover, Germany.
Susann DehmelFraunhofer Institute of Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) of the German Center for Lung Research (DZL), Hannover, Germany.
Yuran XieDepartment of Oncology, Wayne State University School of Medicine, 4100 John R St, Detroit, MI 48201, United States.
Aditi MehtaDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University of Munich, Butenandtstraße 5, 81377 Munich, Germany; Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Munich, German Center for Lung Research (DZL), Munich, Germany.
Katherina SewaldFraunhofer Institute of Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) of the German Center for Lung Research (DZL), Hannover, Germany.
Olivia M MerkelDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University of Munich, Butenandtstraße 5, 81377 Munich, Germany; Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Munich, German Center for Lung Research (DZL), Munich, Germany. Electronic address: Olivia.merkel@lmu.de.
Ludwig-Maximilians-Universität München · DEGerman Center for Lung Research · DEFraunhofer Institute for Toxicology and Experimental Medicine · DEWayne State University · US

Funding

European Research Council 637830
6 · The paper itself

Abstract

GATA3 gene silencing in activated T cells displays a promising option to early-on undermine pathological pathways in the disease formation of allergic asthma. The central transcription factor of T helper 2 (Th2) cell cytokines IL-4, IL-5, and IL-13 plays a major role in immune and inflammatory cascades underlying asthmatic processes in the airways. Pulmonary delivery of small interfering RNAs (siRNA) to induce GATA3 knockdown within disease related T cells of asthmatic lungs via RNA interference (RNAi) presents an auspicious base to realize this strategy, however, still faces some major hurdles. Main obstacles for successful siRNA delivery in general comprise stability and targeting issues, while in addition the transfection of T cells presents a particularly challenging task itself. In previous studies, we have developed and advanced an eligible siRNA delivery system composed of polyethylenimine (PEI) as polycationic carrier, transferrin (Tf) as targeting ligand and melittin (Mel) as endosomolytic agent. Resulting Tf-Mel-PEI polyplexes exhibited ideal characteristics for targeted siRNA delivery to activated T cells and achieved efficient and sequence-specific gene knockdown in vitro. In this work, the therapeutic potential of this carrier system was evaluated in an optimized cellular model displaying the activated status of asthmatic T cells. Moreover, a suitable siRNA sequence combination was found for effective gene silencing of GATA3. To confirm the translatability of our findings, Tf-Mel-PEI polyplexes were additionally tested ex vivo in activated human precision-cut lung slices (PCLS). Here, the formulation showed a safe profile as well as successful delivery to the lung epithelium with 88% GATA3 silencing in lung explants. These findings support the feasibility of Tf-Mel-PEI as siRNA delivery system for targeted gene knockdown in activated T cells as a potential novel therapy for allergic asthma.

Indexed as

AsthmaLungGATA3 Transcription FactorHumansPolyethyleneimineRNA, Double-StrandedRNA InterferenceRNA, Small InterferingTransferrinGATA3 protein, humanGATA3 Transcription FactorPolyethyleneimineRNA, Double-StrandedRNA, Small InterferingTransferrinAsthmaCytokinesPCLSPulmonary deliverysiRNA therapyT cell targeting

Identifiers

PMID36634709
PMCPMC7614985
OpenAlexW4315927712

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.