Oligopeptide-terminated poly(β-amino ester)s for highly efficient gene delivery and intracellular localization

Nathaly Segovia, Pere Dosta, Anna Cascante, Victor Ramos, Salvador Borrós

Producció científica: Article en revista indexadaArticleAvaluat per experts

63 Cites (Scopus)

Resum

The main limitation of gene therapy towards clinics is the lack of robust, safe and efficient gene delivery vectors. This paper describes new polycations for gene delivery based on poly(β-amino ester)s (pBAE) containing terminal oligopeptides. The authors developed oligopeptide-modified pBAE-pDNA nanoparticles that achieve better cellular viability and higher transfection efficacy than other end-modified pBAE and commercial transfection agents. Gene expression in highly permissive cell lines was remarkably high, but transfection efficiency in less-permissive cell lines was highly dependent on oligopeptide composition and nanoparticle formulation. Moreover, the use of selected oligopeptides in the pBAE formulation led to preferential intracellular localization of the particles. Particle analysis of highly efficient pBAE formulations revealed different particle sizes and charge features, which indicates chemical pseudotyping of the particle surface, related to the oligopeptide chemical nature. In conclusion, chemical modification at the termini of pBAE with amine-rich oligopeptides is a powerful strategy for developing delivery systems for future gene therapy applications.

Idioma originalAnglès
Pàgines (de-a)2147-2158
Nombre de pàgines12
RevistaActa Biomaterialia
Volum10
Número5
DOIs
Estat de la publicacióPublicada - de maig 2014

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