Project description
In silico design and experimental assessment of RNA therapeutics for lung diseases
RNA therapeutics are a new class of drugs that use RNA molecules to treat or prevent diseases. RNA interference therapeutics are based on a natural mechanism for silencing specific genes. Despite the potential of RNA therapy to treat undruggable targets in the lung, existing RNA formulations are unstable for inhaled delivery. Funded by the European Research Council, the RatInhalRNA project aims to improve RNA therapy for pulmonary disorders. Researchers will employ molecular dynamics and machine learning strategies in combination with polymer synthesis and physico-chemical characterisation to optimise nanoparticles for the pulmonary delivery of RNA therapeutics.
Objective
The overarching goal of RatInhalRNA is to computationally predict and develop efficient formulations for pulmonary RNA therapy. New RNA formulations are imperative for clinical RNA delivery beyond the liver. The lung offers undruggable targets which could be treated with RNA therapeutics. However, approved siRNA formulations are not suited for pulmonary delivery due to instability in lung surfactant and during nebulization. Hence, it is my aim to rationally design inhalable and biocompatible polymer-based siRNA formulations for efficient siRNA delivery to the lung.
While biomaterials are commonly optimized empirically via one-variable-at-a-time experimentation, I am the first to combine Design-of-Experiments (DoE) with Molecular Dynamics (MD) Simulations and Machine Learning (ML) to accelerate the discovery and optimization process of siRNA nanocarriers towards the metrics of gene silencing efficacy and biocompatibility at reduced wet-lab resources.
In RatInhalRNA, I will synthesize amphiphilic polyspermines and will prepare siRNA-loaded nanoparticles by microfluidic assembly for experimental assessment of physico-chemical parameters as well as in vitro and in vivo gene silencing efficacy in coronavirus infection models. I will assess siRNA binding of the polyspermines via MD simulations and will analyze the contribution of the nanoparticle design factors on experimental and computational readout responses of the DoE. I will train a support vector machine for supervised ML and will generate models to identify areas of interest. Based on the predictions, I will test additional formulations to obtain a validation dataset for the assessment the ability of the ML algorithm to identify design properties of efficient siRNA nanoparticles for pulmonary delivery.
RatInhalRNA will enable me to predict favorable siRNA nanoparticle characteristics in the future prior to polymer synthesis thereby reducing experimental work and improving sustainability and animal welfare.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences chemical sciences polymer sciences
- medical and health sciences health sciences infectious diseases RNA viruses coronaviruses
- natural sciences biological sciences genetics RNA
- engineering and technology nanotechnology nano-materials
- engineering and technology industrial biotechnology biomaterials
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
80539 MUNCHEN
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.