title: Gemini surfactants mediate efficient mitochondrial gene delivery and expression.
abstract: 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.
authors: CNC-Center for Neuroscience and Cell Biology, ‡Department of Life Sciences, and §Faculty of Pharmacy, University of Coimbra , Coimbra, Portugal.
authors: Ana M
authors: AM
authors: Cardoso
authors: Catarina M
authors: CM
authors: Morais
authors: A Rita
authors: AR
authors: Cruz
authors: Ana L
authors: AL
authors: Cardoso
authors: Sandra G
authors: SG
authors: Silva
authors: M Luísa
authors: ML
authors: do Vale
authors: Eduardo F
authors: EF
authors: Marques
authors: Maria C
authors: MC
authors: Pedroso de Lima
authors: Amália S
authors: AS
authors: Jurado
mesh_terms: D000475:Alkenes / Q000737:chemistry; D005454:Fluorescence Polarization; D015870:Gene Expression; D018014:Gene Transfer Techniques; D050259:Genes, Mitochondrial; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000475:Alkenes; D008563:Membrane Lipids; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; D013501:Surface-Active Agents; D049452:Green Fluorescent Proteins
keywords: complex size; complex surface charge; complex−membrane interactions; gemini surfactants; mitochondria; serine; transfection