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Novel asthma therapy SIGNED

Biocompatible nanoparticles for T cell targeted siRNA delivery as novel asthma therapy

Total Cost €


EC-Contrib. €






 Novel asthma therapy project word cloud

Explore the words cloud of the Novel asthma therapy project. It provides you a very rough idea of what is the project "Novel asthma therapy" about.

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Project "Novel asthma therapy" data sheet

The following table provides information about the project.


Organization address
postcode: 80539

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-10-01   to  2021-12-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

The aim of this proposal is to engineer biocompatible nanoparticles that deliver short interfering RNA (siRNA) to activated T cells (ATCs) for the downregulation of the Type 2 T helper cell (Th2) transcription factor GATA-3. By downregulating GATA-3 with siRNA, which regulates the secretion of proinflammatory cytokines in chronic inflammatory diseases such as asthma, the activation of their downstream inflammatory cascades can be prevented. However, T cells are hard-to-transfect cells which are not readily accessible for nucleic acid based therapeutics. I am the first to have demonstrated successful and targeted siRNA delivery to ATCs ex vivo and in vivo for specific GATA-3 knockdown without delivering siRNA to naive T cells. Thus, I can avoid general immune suppression. This was achieved by engineering targeted siRNA delivery systems based on low molecular weight polyethylenimine (LMW-PEI) which form nanoparticles with siRNA and successfully deliver the latter to ATCs. The targeting approach was realized by coupling transferrin to LMW-PEI and by optimizing the coupling chemistry. I have demonstrated specific delivery to ATCs in a mouse model of allergic asthma and have screened siRNA sequences for efficient GATA-3 knockdown. The nanoparticles were administered locally to the lung to prevent the first-pass effect in the liver. The LMW-PEI based nanocarriers were very well tolerated in healthy animals, however, potentially caused additional proinflammatory effects in the asthma model. Therefore, I will engineer nanocarriers that do not only specifically deliver siRNA to ATCs but are also biocompatible in a diseased state of the lung. I will use oligospermines, which are tetramers and octamers of spermine, an endogenous polyamine, and apply the optimized coupling strategy to target the spermine based nanocarriers to ATCs for therapeutic GATA-3 knockdown. To obtain clinically relevant formulations, I will produce inhalable powders of these nanocarriers.


year authors and title journal last update
List of publications.
2018 Daniel P. Feldmann, Yilong Cheng, Rima Kandil, Yuran Xie, Mariam Mohammadi, Hartmann Harz, Akhil Sharma, David J. Peeler, Anna Moszczynska, Heinrich Leonhardt, Suzie H. Pun, Olivia M. Merkel
In vitro and in vivo delivery of siRNA via VIPER polymer system to lung cells
published pages: 50-58, ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2018.02.017
Journal of Controlled Release 276 2019-11-26
2018 Elena Dalle Vedove, Gabriella Costabile, Olivia M. Merkel
Mannose and Mannose-6-Phosphate Receptor-Targeted Drug Delivery Systems and Their Application in Cancer Therapy
published pages: 1701398, ISSN: 2192-2640, DOI: 10.1002/adhm.201701398
Advanced Healthcare Materials 2019-11-26
2017 Daniel P Feldmann, Yuran Xie, Steven K Jones, Dongyue Yu, Anna Moszczynska, Olivia M Merkel
The impact of microfluidic mixing of triblock micelleplexes on in vitro $/$ in vivo gene silencing and intracellular trafficking
published pages: 224001, ISSN: 0957-4484, DOI: 10.1088/1361-6528/aa6d15
Nanotechnology 28/22 2019-11-26
2019 Rima Kandil, Olivia M. Merkel
Recent progress of polymeric nanogels for gene delivery
published pages: 11-23, ISSN: 1359-0294, DOI: 10.1016/j.cocis.2019.01.005
Current Opinion in Colloid & Interface Science 39 2019-11-26
2018 Rima Kandil, Daniel Feldmann, Yuran Xie, Olivia M. Merkel
Evaluating the Regulation of Cytokine Levels After siRNA Treatment in Antigen-Specific Target Cell Populations via Intracellular Staining
published pages: 323-331, ISSN: , DOI: 10.1007/978-1-4939-9092-4_21
Handbook of Experimental Pharmacology 2019-11-26
2016 Qian Zhong, Olivia M. Merkel, Joshua J. Reineke, Sandro R. P. da Rocha
Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution
published pages: 1866-1878, ISSN: 1543-8384, DOI: 10.1021/acs.molpharmaceut.6b00036
Molecular Pharmaceutics 13/6 2019-11-26
2016 Yuran Xie, Bryan Killinger, Anna Moszczynska, Olivia Merkel
Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
published pages: 1334, ISSN: 1420-3049, DOI: 10.3390/molecules21101334
Molecules 21/10 2019-11-26
2016 Yuran Xie, Na Hyung Kim, Venkatareddy Nadithe, Dana Schalk, Archana Thakur, Ayşe Kılıç, Lawrence G. Lum, David J.P. Bassett, Olivia M. Merkel
Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma
published pages: 120-129, ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2016.03.029
Journal of Controlled Release 229 2019-11-26
2015 Yuran Xie, Olivia M. Merkel
Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma
published pages: 681-688, ISSN: 0365-6233, DOI: 10.1002/ardp.201500120
Archiv der Pharmazie 348/10 2019-11-26

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