ERC Projects

1. "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:

• Kromer APE, Sieber-Schäfer F, Farfan Benito J, Merkel OM*: Design of Experiments Grants Mechanistic Insights into the Synthesis of Spermine-Containing PBAE Copolymers
  ACS Applied Materials and Interfaces 2024, ahead of print, ​​doi: 10.1021/acsami.4c06079

• Jin Y, Wang X, Kromer APE, Müller J, Zimmermann C, Xu Z, Hartschuh A, Adams F, Merkel OM: Role of Hydrophobic Modification in Spermine-Based Poly(β-amino ester)s for siRNA Delivery and Their Spray-Dried Powders for Inhalation and Improved Storage
  Biomacromolecules 2024, ahead of print, doi: 10.1021/acs.biomac.4c00283

• Jonas Binder, Joshua Winkeljann, Katharina Steinegger, Lara Trnovec, Daria Orekhova, Jonas Zähringer, Andreas Hörner, Valentin Fell, Philip Tinnefeld, Benjamin Winkeljann, Wolfgang Frieß, Olivia M Merkel, Olivia M Merkel*: Pulmonary siRNA Delivery with Sophisticated Amphiphilic Poly(Spermine Acrylamides) for the Treatment of Lung Fibrosis. Closing the Gap between Experiment and Simulation─ A Holistic Study on the Complexation of Small Interfering RNAs with Polyethylenimine.
  Molecular Pharmaceutics 2024, doi:10.1021/acs.molpharmaceut.3c00747

• 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

2. "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: Evaluation of the effects of storage conditions on spray-dried siRNA-LNPs before and after subsequent drying. European Journal of Pharmaceutics and Biopharmaceutics, 2023, 193: 218-226

• 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

3. "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:

• Jin Y, Wang X, Kromer APE, Müller J, Zimmermann C, Xu Z, Hartschuh A, Adams F, Merkel OM: Role of Hydrophobic Modification in Spermine-Based Poly(β-amino ester)s for siRNA Delivery and Their Spray-Dried Powders for Inhalation and Improved Storage
  Biomacromolecules 2024, ahead of print, doi: 10.1021/acs.biomac.4c00283

• David C. Jürgens, Joschka T. Müller, Anny Nguyen, Olivia M Merkel*: Tailoring lipid nanoparticles for T-cell targeting in allergic asthma: Insights into efficacy and specificity.
  European Journal of Pharmaceutics and Biopharmaceutics 2024, 198: 114242

• Friederike Adams, Christoph M Zimmermann, Domizia Baldassi, Thomas M Pehl, Philipp Weingarten, Iris Kachel, Moritz Kränzlein, David C Jürgens, Peter Braubach, Ioannis Alexopoulos, Malgorzata Wygrecka, Olivia M Merkel*: Pulmonary siRNA Delivery with Sophisticated Amphiphilic Poly(Spermine Acrylamides) for the Treatment of Lung Fibrosis.
  Small, 2023, e2308775. doi: 10.1002/smll.202308775.

• Yao Jin, Friederike Adams, Anny Nguyen, Sebastian Sturm, Simone Carneiro, Olivia M Merkel*: Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery.
  Nanoscale Advances, 2023, 5 (19): 5256-5262

• 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.