Synergistic effects on gene delivery - co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000 (TM)

This paper describes the application of gene delivery vectors based on connecting together two well-defined low-generation poly(L-lysine) (PLL) dendrons using a disulfide-containing linker unit. We report that the transfection ability of these vectors in their own right is relatively low, because the low-generation number limits the endosomal buffering capacity. Importantly, however, we demonstrate that when applied in combination with Lipofectamine 2000 (TM), a vector from the cationic lipid family, these small cationic additives significantly enhance the levels of gene delivery (up to four-fold). Notably, the cationic additives have no effect on the levels of transfection observed with a cationic polymer, such as DEAE dextran. We therefore argue that the synergistic effects observed with Lipofectamine 2000 (TM) arise as a result of combining the delivery advantages of two different classes of vector within a single formulation, with our dendritic additives providing a degree of pH buffering within the endosome. As such, the data we present indicate that small dendritic structures, although previously largely overlooked for gene delivery owing to their inability to transfect in their own right, may actually be useful well-defined additives to well-established vector systems in order to enhance the gene delivery payload.

Access to a Car and the Self-Reported Health and Mental Health of People Aged 65 and Older in Northern Ireland

This article examines relationships between access to a car and the self- reported health and mental health of older people. The analysis is based on a sample of N 1⁄4 65,601 individuals aged 65 years and older from the Northern Ireland Longitudinal Study linked to 2001 and 2011 census returns. The findings from hierarchical linear and binary logistic multilevel path models indicate that having no access to a car is related to a considerable health and mental health disadvantage particularly for older people who live alone. Rural–urban health and mental health differences are mediated by access to a car. The findings support approaches that emphasize the importance of autonomy and independence for the well-being of older people and indicate that not having access to a car can be a problem for older people not only in rural but also in intermediate and urban areas, if no sufficient alternative forms of mobility are provided.