Novel strategy to disrupt the nuclear pore barrier reversibly: Implications for nanomedicine

Conference Dates

July 3-7, 2016


Several thousands of nuclear pore complexes (NPCs) perforate the nuclear envelope of each eukaryotic cell. These elaborate proteinaceous assemblies mediate all nucleocytoplasmic transport highly selectively through a central channel residing within a rigid and well-structured NPC scaffold. The selectivity of the NPCs is the major obstacle for non-viral gene therapy due to the prevention of exogenously applied therapeutic macromolecules from nuclear entry. Selectivity is attributed to highly dynamic and disordered Phenylalanine-Glycine rich proteins within the NPC central channel. The NPC scaffold poses an additional barrier-albeit ignored so far. We designed two distinct strategies to reversibly disrupt the NPC channel and scaffold in a separate fashion. Disruption of either is found to result in a significant increase of the NPC permeability and a combination of the two further intensifies the individual effects. The induced breakdown of the NPC permeability barrier may be exploited for gene therapeutic purposes.

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