Advanced search
Start date
Betweenand

Complex coacervate core micelles and polyelectrolyte complexes for gene therapies: unrevealing thermodynamics and structural features, optimizing biological responses

Grant number: 22/13895-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): February 01, 2023
Effective date (End): January 31, 2024
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
Principal Investigator:Watson Loh
Grantee:João Pedro Elias Machado
Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:21/12071-6 - Tailoring colloids through supramolecular interactions: from fundamentals to applications, AP.TEM

Abstract

The scope of this project is the design and synthesis of novel polymeric vectors (polycations and ionic-neutral block copolymers) towards the formulation of DNA- and RNA-based polyelectrolyte complexes and complex coacervates core micelles focusing on applications within the framework of gene carriers. Gene delivery using non-viral vectors is a multi-step process that currently poses many challenges and the successful medical developments still requires substantial fundamental research. Primarily, the cationic entities have to be able to bind to the phosphodiester backbones of nucleic acids thereby forming supramolecular complexes, thus protecting the polynucleotides at physiological conditions, for instance, from nuclease digestion. Nevertheless, after transfection to the intercellular environment, the supramolecular assemblies have to be unpacked and, at this stage, instead of stability, lability is desired because the dissociation of the complexes is essential to enable the therapeutic activity of the nucleic acids. Although the efforts to manufacture DNA and RNA-based nanoparticles with enhanced efficacy have focused essentially on keeping fishing potential polycation and derivatives, sometimes in a lottery fashion. To avoid this, the understanding the mechanism of interaction, for instance via the thermodynamics of binding, as well as effects of nanoparticle´s composition, are highly recommended because they are certainly connected to the different levels of transfection efficiency. Therefore, this proposal seeks the desing of novel polymer-based complexing agents to provide new formulations for gene therapy. To achieve this main goal, it will be necessary to control and understand fundamentally the influence of different polymer architectures and chemical nature on the nucleic acid binding. Then, the buffering capacity of the complexing agents will be determined by pH titration and the nanoparticles will be studied by scattering techniques. Finally, the selected formulations will be evaluated biologically from the point of view of cytotoxicity, cellular uptake, intracellular trafficking and gene transfection efficiency. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list using this form.