Nuclear proteins as gene-transfer vectors

An interest in nuclear proteins as possible gene vectors arose as early as 1988. Nuclear proteins possess important features, such as DNA condensing capacity and the presence of NLSs (nuclear localization signals), which are thought to be perfect tools to combine cellular and nuclear uptake of DNA. The NLS of the proteins might support the intracellular trafficking of the complexes, whereas their condensing capacity enables DNase stability. Nuclear proteins, histones and also non-histones, such as the high-mobility-group proteins, have been successfully employed in in vitro gene transfer by a variety of workers over the last decade. In the pertinent published data, almost all nuclear proteins tested showed gene-transfer activity. The degree of activity of the individual nuclear proteins tested varied according to sequential and structural differences of the proteins, discriminating their DNA binding behaviour, but reported transfection efficiency differences are inconsistent. They do not reveal a logical pattern, such as a correlation with their DNA affinity. The differences in transfection efficiency of certain nuclear proteins reported by different authors could be based on a lot of factors, including the source or method of protein preparation, the cells used, the media or the transfection additives, such as lysosomotropic agents. The variances are quite random, which suggests an involvement of physicochemical parameters of the nuclear protein-DNA complexes in the efficiency of gene expression. Physicochemical features of the complexes are also determined by factors such as transfection additives (e.g. Ca2+). The present review therefore includes, in addition to an overview about the nuclear proteins used in gene-transfer experiments, some assumptions about the mechanism of the cellular uptake of nuclear protein-DNA complexes and their translocation to the nucleus.