Gemini Surfactants Mediate Efficient Mitochondrial Gene Delivery and Expression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Ana M Cardoso (Autor) Outra; Catarina M Morais (Autor) Outra; Rita Cruz, AR (Autor) Outra; Ana L Cardoso (Autor) Outra; Sandra G Silva (Autor) Outra; Luisa do Vale, ML (Autor) FCUP; Eduardo F Marques (Autor) FCUP; Maria C P Pedroso de Lima (Autor) Outra; Amalia S Jurado (Autor) Outra

Revista

Título: Molecular Pharmaceutics

Vol. 12 Nº 6

Páginas: 716-730

ISSN: 1543-8384

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 47 Citações

Scopus - 54 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: P-00A-7TH

DOI: 10.1021/mp5005349

Abstract (EN): Gene delivery targeting mitochondria has the potential to transform the therapeutic landscape of mitochondrial genetic diseases. Taking advantage of the nonuniversal genetic code used by mitochondria, a plasmid DNA construct able to be specifically expressed in these organelles was designed by including a codon, which codes for an amino acid only if read by the mitochondrial ribosomes. In the present work, gemini surfactants were shown to successfully deliver plasmid DNA to mitochondria. Gemini surfactant-based DNA complexes were taken up by cells through a variety of routes, including endocytic pathways, and showed propensity for inducing membrane destabilization under acidic conditions, thus facilitating cytoplasmic release of DNA. Furthermore, the complexes interacted extensively with lipid membrane models mimicking the composition of the mitochondrial membrane, which predicts a favored interaction of the complexes with mitochondria in the intracellular environment. This work unravels new possibilities for gene therapy toward mitochondrial diseases.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15