Cationic lipids nowadays constitute a promising alternative to recombinant viruses for gene transfer. We have recently explored the transfection potential of a new class of lipids based upon the use of aminoglycosides as cationic polar headgroups. The encouraging results obtained with a first cholesterol derivative of kanamycin A prompted us to investigate this family of vectors further, by modulating the constituent structural units of the cationic lipid. For this study, we have investigated the transfection properties of a series of new derivatives based on a kanamycin A scaffold. The results primarily confirm that aminoglycoside-based lipids are efficient vectors for gene transfection both in vitro and in vivo (mouse airways). Furthermore, a combination of transfection and physicochemical data revealed that some modifications of the constitutive subunits of kanamycin A-based vectors were associated with substantial changes in their transfection properties.
We evaluated the effects of polymorphic markers within the b globin gene cluster on HbF expression in two groups. These groups were randomly selected from a survey of HbF distribution in a large population study of unrelated healthy Algerian adults (n=827). The first group contained individuals with normal HbF levels (0.1 ± 0.5%) and the second group contained individuals with raised HbF levels (0.8 ± 2.3%). Of the various polymorphic markers analysed, only the 7309 Gg A?G, the 7158 Gg C?T, the Gg IVS2 TC (TG) 9 AG (TG) 2 (CG) 2 and the 7540 b (AT) 9 T 5 sequence configurations were significantly associated with increased HbF levels. More than 84% of the subjects with elevated HbF levels carried one or several of these four marker configurations, suggesting that the b globin gene cluster exerts a significant effect on HbF expression in healthy individuals.
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