RT Journal Article
T1 Transgene expression in mice of the Opa1 mitochondrial transmembrane protein through bicontinuous cubic lipoplexes containing gemini imidazolium surfactants
A1 Muñoz Úbeda, Mónica
A1 Semenzato, Martina
A1 Franco‑Romero; Anais, 
A1 Junquera González, María Elena
A1 Aicart Sospedra, Emilio
A1 Scorrano, Luca
A1 López Montero, Iván
AB Background: Lipoplexes are non-viral vectors based on cationic lipids used to  deliver DNA into cells, also known as lipofection. The positively charge of the hydrophilic head-group provides the cationic lipids the ability to condensate the negatively charged DNA into structured complexes. The polar head can carry a large variety of chemical groups including amines as well as guanidino or imidazole groups. In particular, gemini cationic lipids consist of two positive polar heads linked by a spacer with different length. As for the hydrophobic aliphatic chains, they can be unsaturated or saturated and are connected to the polar head-groups. Many other chemical components can be included in the formulation of lipoplexes to improve their transfection efficiency, which often relies on their structural features. Varying these components can drastically change the arrangement of DNA molecules within the lamellar, hexagonal or cubic phases that are provided by the lipid matrix. Lipofection is widely used to deliver genetic material in cell culture experiments but the simpler formulations exhibit major drawbacks related to low transfection, low specificity, low circulation half-life and toxicity when scaled up to in vivo experiments. Results: So far, we have explored in cell cultures the transfection ability of lipoplexes based on gemini cationic lipids that consist of two C16 alkyl chains and two imidazolium polar head-groups linked with a polyoxyethylene spacer, (C16Im)2(C4O). Here, PEGylated lipids have been introduced to the lipoplex formulation and the transgene expression of the Opa1 mitochondrial transmembrane protein in mice was assessed. The addition of PEG on the surface of the lipid mixed resulted in the formation of Ia3d bicontinuous cubic phases as determined by small angle X-ray scattering. After a single intramuscular administration, the cubic lipoplexes were accumulated in tissues with tight endothelial barriers such as brain, heart, and lungs for at least 48 h. The transgene expression of Opa1 in those organs was identified by western blotting or RNA expression analysis through quantitative polymerase chain reaction.Conclusions: The expression reported here is sufficient in magnitude, duration and toxicity to consolidate the bicontinuous cubic structures formed by ( C16Im)2(C4O)-based lipoplexes as valuable therapeutic agents in the field of gene delivery.
PB BMC
SN 1477-3155
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/108995
UL https://hdl.handle.net/20.500.14352/108995
LA eng
NO Muñoz-Úbeda M, Semenzato M, Franco-Romero A, Junquera E, Aicart E, Scorrano L, et al. Transgene expression in mice of the Opa1 mitochondrial transmembrane protein through bicontinuous cubic lipoplexes containing gemini imidazolium surfactants. J Nanobiotechnol 2021;19:425. https://doi.org/10.1186/s12951-021-01167-x.
NO Ministerio de Ciencia, Innovación y Universidades
NO Universidad Complutense de Madrid
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 9 abr 2025