Drug Discovery in Preclinical Research (Track)


Zakaria A. Almsherqi and Deng Yuru

Physiology Department, National University of Singapore, Singapore


Currently established DNA transfection agents including virus particles and cationic lipids are characterized by substantial cytotoxicity and limited efficiency. We developed and exploited a novel DNA transfection agent of biological origin: Cubic Membranes, which are highly ordered, macroporous liquid crystalline structures found within a variety of organisms. In previous studies we have shown that inner mitochondrial membranes of starved amoeba (Chaos carolinense) adopt cubic morphology. These mitochondria with cubic membrane organization passively take up DNA oligonucleotides (ODNs) and that these ODNs-membrane complexes are readily internalized within the cytoplasm of cultured mammalian cells.

Simple mixing of the total lipids extracted from cubic membranes with water (liposomal reconstruction) exhibit cubic morphology (called cubosomes) similar to cubic membrane organization. This observation encourages us to test if cubic membrane-extracted lipids would have the same property of cubic membranes to take up and retain ODNs. Our experimental data support the suggested ability of cubic membrane-extracted lipids to act as a vehicle for gene transfection. Furthermore, detailed analysis of cubic membrane-derived lipids shows very low levels of cationic lipids (which could reduce the risk of cytotoxicity) and high content of plasmologens (which may enhances cellular uptake and intracellular release of the genetic material). Thus, cubic membranes and/or the lipids extracted from cubic membranes may offer novel gene delivery systems with higher efficacy and lower cytotoxicity compared to current commercially available methods and techniques based on cationic lipoplexes.

Keywords: Gene therapy, Cubic membrane, Cubic phase, Non-viral vector, Transfection