A light-activatable nanoparticle library for the delivery of RNA-based therapies


Project Summary

Impaired wound healing and its medical complications remain one of the most prevalent and economically burdensome healthcare issues in the world. RNA-based therapies have emerged recently as promising drugs for skin regeneration. RNA-based therapies have some distinct advantages over conventional drug therapies such as small molecules or other biomolecules, such as specificity, potency, number of accessible targets, species crossreactivity, manufacturing, etc… However, several obstacles need to be addressed before the clinical translation of RNA-based therapeutics, in particular, the design of formulations that enable their delivery to a target cell in the skin reducing potential off-target effects and simultaneously to increase their efficacy in the intracellular delivery. In this project, we aim at developing a NP library to identify hits with improved in vitro the intracellular delivery of RNA-based therapeutics and to demonstrate in vivo the therapeutic effect in a wound healing animal model. The project combines NP synthesis, high-throughput analyses, biological activity tests either in vitro or in vivo and integrates a multi-disciplinary team formed by academics from Portugal, a clinician from the largest institution treating chronic wounds in Portugal (APDP) and a large pharmaceutical company (Astrazeneca). The project will contribute for the advance of our knowledge in RNA-based therapeutics delivery, advanced NP formulations and wound healing.

Main Goals

The main goals of the project are: (i) create a library of polymeric light-activatable NPs; (ii) identify NP formulations having higher knockdown properties than commercial transfection agents and to evaluate the underline mechanism; (iii) evaluate in vivo the therapeutic effect of the best siRNA-loaded NPs formulations and to compare it with conventional delivery approaches (e.g. administration of siRNA by lipofectamine).

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