Factors influencing the nuclear targeting ability of nuclear localization signals

A nuclear localization signal (NLS) is a short amino acid sequence derived from eukaryotic nuclear proteins and viral proteins. Many NLS peptides can efficiently mediate the intranucleus transport of cargo molecules, so they have been widely used for non-viral gene transfer and shown potential ability to improve nuclear delivery of DNA. In order to maximally utilize NLS peptides to enhance gene transfer, several factors such as methods of incorporating NLS peptide, type and property of NLS peptide, number of NLS peptide, and spacer between NLS peptide and DNA should be considered. This review article summarizes how these factors influence the ability of NLS peptides in enhancing non-viral gene delivery and aids in defining the requirements for successful NLS-enhanced transfection.