Gemini Surfactants Mediate Efficient Mitochondrial Gene Delivery and Expression

• Type: Article in International Scientific Journal
• Date: 2015

Authors

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

Journal

Title: Molecular Pharmaceutics

Vol. 12 No. 6

Pages: 716-730

ISSN: 1543-8384

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 47 Citations

Scopus - 54 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15