Evidence map›Paper›PMID 31372493›Full record

ArticleAdvanced therapeutics2019

Coming in and Finding Out: Blending Receptor-Targeted Delivery and Efficient Endosomal Escape in a Novel Bio-Responsive siRNA Delivery System for Gene Knockdown in Pulmonary T Cells.

Rima Kandil, Yuran Xie, Ralf Heermann, Lorenz Isert, Kirsten Jung, Aditi Mehta, Olivia M Merkel

Open access · greenAbstract read
In one paragraph

Article in Advanced therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Recent Update on siRNA Therapeutics.International journal of molecular sciences · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. 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
  9. Review
  10. Article
  11. Article
  12. Review
  13. Targeted GATA3 knockdown in activated T cells via pulmonary siRNA delivery as novel therapy for allergic asthma.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  14. Engineering poly- and micelleplexes for nucleic acid delivery - A reflection on their endosomal escape.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
  15. Review
  16. Evaluation of adsorption of DNA/PEI polyplexes to tubing materials.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2022
    Article
  17. Article
  18. Article
  19. Article
  20. Review
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

7 authors at 3 institutions in 2 countries.

Rima KandilDepartment of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig-Maximilians-University, Butenandtstraße 5-13, 81337 Munich, Germany.
Yuran XieDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, USA.
Ralf HeermannInstitute for Molecular Physiology, Microbiology and Wine Research, Johannes-Gutenberg-University, Johann-Joachim-Becher-Weg 13, 55128 Mainz, Germany; Biocenter, Department Microbiology, Ludwig-Maximilians-University, Großhaderner Str. 2-4, 82152 Martinsried, Germany.
Lorenz IsertDepartment of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig-Maximilians-University, Butenandtstraße 5-13, 81337 Munich, Germany.
Kirsten JungBiocenter, Department Microbiology, Ludwig-Maximilians-University, Großhaderner Str. 2-4, 82152 Martinsried, Germany.
Aditi MehtaDepartment of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig-Maximilians-University, Butenandtstraße 5-13, 81337 Munich, Germany.
Olivia M MerkelDepartment of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig-Maximilians-University, Butenandtstraße 5-13, 81337 Munich, Germany.
Ludwig-Maximilians-Universität München · DEEugene Applebaum College of Pharmacy and Health Sciences · USJohannes Gutenberg University Mainz · DE

Funding

European Research Council 637830
6 · The paper itself

Abstract

RNA interference (RNAi) offers the potential to selectively silence disease-related genes in defined cell subsets. Translation into the clinical routine is, however, still hampered by the lack of efficient carrier systems for therapeutic siRNA, endosomal entrapment presenting a major hurdle. A promising siRNA delivery system has previously been developed on the base of polyethylenimine (PEI) and the targeting ligand transferrin (Tf) to specifically reach activated T cells in the lung. In the present work, the focus is on optimizing Tf-PEI polyplexes for gene knockdown in primary activated T cells by improving their endosomal escape properties. Blending of the conjugate with membrane lytic melittin significantly enhanced endosomal release and thereby cytoplasmic delivery, while maintaining selective T cell targeting abilities and overall cell tolerability. The gathered data furthermore demonstrate that melittin addition also distinctly improves several other essential particle characteristics, such as siRNA encapsulation efficiency and stability in lung lining fluids. In conclusion, this results in a novel upgraded siRNA delivery system that is not only able to specifically deliver its payload to the desired target cells via receptor-mediated endocytosis, but also shows enhanced release from endosomal vesicles in order to initiate RNAi in the cytoplasm.

Indexed as

endosomal escapemelittinsiRNA deliveryT cell targetingtransferrin receptors

Identifiers

PMID31372493
PMCPMC6675603
OpenAlexW2942302492

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.