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Characterisation and design of RNA-lipid interactions for RNA therapeutics

Project description

Insight into the spatial organisation of RNA

RNA is a vital biomolecule that plays key roles in coding, decoding, regulation and expression of genes. Understanding the control of its bioactivity is thus essential. While much is known about RNA spatial organisation via RNA-protein interactions, other mechanisms remain less explored. Funded by the Marie Skłodowska-Curie Actions programme, the RNA-lipid project focuses on lipid membranes serving as scaffolds for RNA. Researchers aim to develop membrane-binding RNAs and investigate their binding mechanisms, selectivity and stability. The goal is to organise protein expression by introducing these lipid-binding RNAs into mRNAs and improve stability of RNA therapeutics.

Objective

RNA is a ubiquitous biomolecule with a broad range of activities crucial for keeping cells alive. Understanding how RNA bioactivity is controlled is vital for elucidating its roles and applications in molecular biology. RNA, in order to maintain a correct activity patterns, has to be organized. Despite sufficient knowledge about RNA spatial organization within cells via RNA-protein interaction-based processes not much is known about other mechanisms. Revealing the RNA-localization patterns without RNA-binding proteins would create the new branch of interactomics which might have significant implications in the molecular biology and RNA-based therapeutics development.
Recently I described that lipid membranes can act as a scaffold for RNAs in a sequence and structure dependent binding process leading to the changes of the RNA activity in vitro. Here, I propose that lipid membranes act as a selective RNA scaffold in vivo. In the following project I will develop a library of membrane-binding RNAs using in vitro selection approach. I will characterize the mechanisms, selectivity, and stability of RNA-lipid binding in bulk and in nano-scale level using self-developed binding assays and super-resolution microscopy, respectively. Furthermore, obtained lipid-binding RNAs are going to be artificially introduced to the existing mRNAs in order to spatially organize protein expression both in vitro and in vivo. The RNA RNA-lipid encapsulation efficiency will be characterized using recently developed single-particle profiling platform. Lastly, I will use gathered knowledge to livetrack the uptake and improve the RNA-based therapeutics (i.e. RNA-lipid nanoparticles) in order to increase the RNA stability and decrease the toxicity of the formulation.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

KAROLINSKA INSTITUTET
Net EU contribution

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.

€ 206 887,68
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

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