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Communication Dans Un Congrès Année : 2022

RNA encapsulation by protein cages

Résumé

RNA based therapies are facing a challenge due to the RNA inherent instability (leverage by the presence of naturally occurring RNAses) and intracellular delivery. An emerging strategy to increase the RNA lifetime and to improve the RNA delivery relies on the use of protein cages . This kind of strategies could be used in several biotechnological and biomedical applications as for example in RNA platforms for storage, transportation and also vaccines design. The encapsulins are protein cages arranged in an icosahedral macromolecular assemblies able to host different kind of naturally occurring cargo proteins (e.g. ferritin like proteins, peroxidases between so many others) . However, not evidence present so far that this versatile protein cages are able to host RNA inside their hollow space. Therefore, we propose, on one hand, to engineering them in order to extend their function by adding RNA binding properties1 . On the other hand, heterologous production of the encapsulins is very challenging, showing so far, a very low yield remaining a limiting factor for their extensive use. So, we are also applying and improving protocols for protein production and purification . The strategy is based on modifying Thermotoga Maritima Encapsulin (Tm.Enc), by adding a RNA binding properties on the pre-folded encapsulin native structure. The selected RNA binding sequences are based on the most conserved aminoacids that present RNA binding proteins in the nature. Then, the selected RNA binding peptides are grafted on the pre-folded encapsulins scaffolds with the help of dedicated protein design and protein structure prediction software as for example Rosetta and Alpha fold respectively. In addition, we are currently optimizing the Encapsulins protein production and purification protocols in the lab and we are planning onto the next step of the project to produce the new of Tm.Enc mutants (not still present in the nature) and assess their respective RNA binding and encapsulation properties.

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Chimie
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Dates et versions

hal-04431382 , version 1 (01-02-2024)

Identifiants

  • HAL Id : hal-04431382 , version 1

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Hitier Casilda, Assrir Nadine, Carine van Heijenoort, Alvarez Lucia, Gauto. Diego. RNA encapsulation by protein cages. Tailoring RNA binding proteins and RNA targeting, Sep 2022, Valencia, Spain. ⟨hal-04431382⟩
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