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  • Title: Novel cholesterol-based cationic lipids for gene delivery.
    Author: Medvedeva DA, Maslov MA, Serikov RN, Morozova NG, Serebrenikova GA, Sheglov DV, Latyshev AV, Vlassov VV, Zenkova MA.
    Journal: J Med Chem; 2009 Nov 12; 52(21):6558-68. PubMed ID: 19824650.
    Abstract:
    Gene therapy based on gene delivery is a promising strategy for the treatment of human disease. Here we present data on structure/biological activity of new biodegradable cholesterol-based cationic lipids with various heterocyclic cationic head groups and linker types. Enhanced accumulation of nucleic acids in the cells mediated by the lipids was demonstrated by fluorescent microscopy and flow cytometry. Light scattering and atomic force microscopy were used to find structure/transfection activity correlations for the lipids. We found that the ability of the lipids to stimulate intracellular accumulation of the oligodeoxyribonucleotides and plasmid DNA correlates well with their ability to form in solution lipid/NA complexes of sizes that do not exceed 100 nm. Screening of the lipids revealed the most promising transfection agents both in terms of low toxicity and efficient delivery: cholesterol-based lipids with positively charged pyridine and methyl imidazole head groups and either the ester or carbamate linker.
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