ERC Projects
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"RatInhalRNA"
Since 2023, we are funded by an ERC Consolidator Grant "RatInhalRNA" to develop inhalable RNA nanocarriers by machine learning and molecular dynamics simulations under grant number ERC-2022-COG-101088587. The project consolidates previous work from our ERC-StG project "Novel Asthma Therapy" with the aim of more rationally designing polymer nanocarriers for RNA by computational and limited experimental work. (Figure credits to Dr. Ben Winkeljann)
https://erc.europa.eu/news-events/news/erc-2022-consolidator-grants-results
The project has a clear aim of reducing wet lab efforts by establishing machine learning algorithms based on experimental data for prediciting improved nanocarriers in a use case of antiviral siRNA against respiratory virus infections.
Project-related publications:
- Domizia Baldassi, Shubhankar Ambike, Martin Feuerherd, Cho-Chin Cheng, David J Peeler, Daniel P Feldmann, Diana Leidy Porras-Gonzalez, Xin Wei, Lea-Adriana Keller, Nikolaus Kneidinger, Mircea Gabriel Stoleriu, Andreas Popp, Gerald Burgstaller, Suzie H Pun, Thomas Michler, Olivia M Merkel*: Inhibition of SARS-CoV-2 replication in the lung with siRNA/VIPER polyplexes. J Control Release 2022 345:661-674. doi: 10.1016/j.jconrel.2022.03.051
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"RNhale"
Since July 2022, we have been funded by an ERC-Proof-of-Concept grant "RNhale" to develop dry powder formulations of RNA-loaded nanoparticles by spray drying under grant number ERC-2022-PoC1-101069308. The project logically builds upon our ERC-StG project "Novel Asthma Therapy" with the aim of refining, translating and exploiting our findings. (Figure credits to Dr. Ben Winkeljann)
https://erc.europa.eu/news/erc-2021-proof-of-concept-grants-results
The project has a clear aim of assessing the commercial positioning of a platform technology for spray-drying RNA and of refining existing protocols for spray-drying RNA NPs made with diverse RNA NPs to overcome current challenges of storage and transport conditions as well as delivery beyond the liver.
Project-related publications:
- Christoph M. Zimmermann et al.: Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery. J Control Release 351:137-150. doi: 10.1016/j.jconrel.2022.09.021
- Tobias W.M. Keil et al.: Impact of Crystalline and Amorphous Matrices on Successful Spray Drying of siRNA Polyplexes for Inhalation of Nano‐in‐Microparticles. Advanced Therapeutics 2021, doi:10.1002/adtp.202100073
- Tobias W. M. Keil, Domizia Baldassi, Olivia M. Merkel, T‐cell targeted pulmonary siRNA delivery for the treatment of asthma, Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 2020, e1634.
- Tobias Keil et al., Characterization of spray dried powders with nucleic acid-containing PEI nanoparticles, European Journal of Pharmaceutics and Biopharmaceutics 2019, 143, 61-69
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"Novel Asthma Therapy"
From October 2015 until December 2021, we developed dry powder platform technologies for targeted pulmonary siRNA delivery to activated T cells in the lung under the ERC Starting Grant ERC-2014-StG – 637830 "Novel Asthma Therapy".
https://erc.europa.eu/projects-and-results/erc-funded-projects/novel-asthma-therapy
http://cordis.europa.eu/project/rcn/198156_en.html
The project had a clear aim of advancing pulmonary nanomedicine as novel asthma therapy specifically and RNA delivery in general.
Project-related publications:
- Rima Kandil, Domizia Baldassi, Sebastian Böhlen, Joschka T Müller, David C Jürgens, Tonia Bargmann, Susann Dehmel, Yuran Xie, Aditi Mehta, Katherina Sewald, Olivia M. Merkel*: Targeted GATA3 knockdown in activated T cells via pulmonary siRNA delivery as novel therapy for allergic asthma. J Control Release 2023, 354:305-315. doi: 10.1016/j.jconrel.2023.01.014.
- Domizia Baldassi, Bettina Gabold, Olivia M. Merkel*: Air−Liquid Interface Cultures of the Healthy and Diseased Human Respiratory Tract: Promises, Challenges, and Future Directions.
Advanced NanoBiomed Research 2021, doi:10.1002/anbr.202000111 - Aditi Mehta, Thomas Michler, Olivia M. Merkel*: siRNA Therapeutics against Respiratory Viral Infections-What Have We Learned for Potential COVID-19 Therapies?
Advanced Healthcare Materials, 2021, e2001650, doi: 10.1002/adhm.202001650. - Tobias W.M. Keil et al.: Impact of Crystalline and Amorphous Matrices on Successful Spray Drying of siRNA Polyplexes for Inhalation of Nano‐in‐Microparticles. Advanced Therapeutics 2021, doi:10.1002/adtp.202100073
- Tobias W. M. Keil, Domizia Baldassi, Olivia M. Merkel, T‐cell targeted pulmonary siRNA delivery for the treatment of asthma, Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 2020, e1634.
- Tobias Keil et al., Characterization of spray dried powders with nucleic acid-containing PEI nanoparticles, European Journal of Pharmaceutics and Biopharmaceutics 2019, 143, 61-69
- Aditi Mehta et al., Targeting KRAS mutant lung cancer cells with siRNA-loaded Bovine Serum Albumin nanoparticles, Pharmaceutical Research 2019, 36, (9), 133
- Rima Kandil et al., 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, Advanced Therapeutics 2019, https://doi.org/10.1002/adtp.201900047
- Daniel P Feldmann et al., In vitro and in vivo delivery of siRNA via VIPER polymer system to lung cells. Journal of Controlled Release 2018, 276, 50-58
- Daniel P. Feldmann et al., The impact of microfluidic mixing of triblock micelleplexes on in vitro/in vivo gene silencing and intracellular trafficking, Nanotechnology 2017, 28(22), 224001.
- Yuran Xie et al., Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine, Molecules 2016, 21(10), 1334.
- Yuran Xie et al., Targeted Delivery of siRNA to Activated T Cells via Transferrin-Polyethylenimine (Tf-PEI) as a Potential Therapy of Asthma, Journal of Controlled Release, 2016, 229, 120-9.
- Yuran Xie and Olivia Merkel, Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma, Archiv der Pharmazie 2015, 348 (19), 681-688.