Nuclear localization signal-tagged systems: relevant nuclear import principles in the context of current therapeutic design
Ritabrita Goswami, Aarohi Gupta, Olga Bednova, Gaël Coulombe, Dipika V. Patel, Vincent M. Rotello, Jeffrey V. Leyton
Abstract
Nuclear targeting of therapeutics provides a strategy for enhancing efficacy of molecules active in the nucleus and minimizing off-target effects. 'Active' nuclear-directed transport and efficient translocations across nuclear pore complexes provide the most effective means of maximizing nuclear localization. Nuclear-targeting systems based on nuclear localization signal (NLS) motifs have progressed significantly since the beginning of the current millennium. Here, we offer a roadmap for understanding the basic mechanisms of nuclear import in the context of actionable therapeutic design for developing NLS-therapeutics with improved treatment efficacy.