Poly(beta-amino ester) based nanoparticles for gene delivery in retinal pigmented epithelium cells (ARPE-19)

Author(s)

Guilherme Capiraço Campese

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2019-02-06

Examining board members

Marcelo Bispo de Jesus; Carmen Veríssima Ferreira; Francisco Benedito Teixeira Pessine

• Advisor: Marcelo Bispo de Jesus

Abstract

Diseases associated with the retina are one of the major causes for visual impairment worldwide of which a variety is genetic. The eye is especially suited for gene therapy interventions due to its relatively easy access, a closed structure and the presence of the blood-retinal barrier. Thus, allowing the development of non-viral vectors capable of altering the genetic profile of retinal cells. However, the lack of understanding about the transfection mechanisms, its correlation with their chemical structure and their nanotoxicological properties has been the bottleneck in the application of those vectors. In this work, polymeric non-viral vectors, made from poly(ß-Amino ester), a biodegradable, pH-sensitive polymer of easy synthesis were synthesized and tested for the delivery of genetic material to retinal pigmented epithelium cells ARPE-19. Using a multiple detection approach, we found an expressive transfection efficiency and low toxicity of the polyplexes. In addition, we have demonstrated that the mass ratio by itself is not enough to explain the transfection efficiency of the polyplexes and that cell division is one of the key events for high transfection rates. Thus, this work sheds light on the mechanisms of transfection of polyplexes made of poly(ß-amino ester) contributing to the advancement in the field of gene therapy interventions of the posterior chamber of the eye (AU)

• FAPESP's process: 16/16259-1 - Bioinspired gene delivery optimization of nanoparticles in retinal pigmented epithelium model
• Grantee: Guilherme Capiraço Campese
• Support Opportunities: Scholarships in Brazil - Master