BioSpace Collaborative - Characterization of Ku702–NLS as Bipartite Nuclear Localization Sequence for Non-Viral Gene Delivery

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Biochemistry - Pediatrics and Child Health

Characterization of Ku702–NLS as Bipartite Nuclear Localization Sequence for Non-Viral Gene Delivery
Published: Wednesday, February 08, 2012
Author: Johannes Matschke et al.

by Johannes Matschke, Alexander Bohla, Christof Maucksch, Rashmi Mittal, Carsten Rudolph, Joseph Rosenecker

Several barriers have to be overcome in order to achieve gene expression in target cells, e.g. cellular uptake, endosomal release and translocation to the nucleus. Nuclear localization sequences (NLS) enhance gene delivery by increasing the uptake of plasmid DNA (pDNA) to the nucleus. So far, only monopartite NLS were analysed for non-viral gene delivery. In this study, we examined the characteristics of a novel bipartite NLS like construct, namely NLS Ku70. We synthesized a dimeric structure of a modified NLS from the Ku70 protein (Ku70₂-NLS), a nuclear transport active mutant of Ku70₂-NLS (s1Ku70₂-NLS) and a nuclear transport deficient mutant of Ku70₂-NLS (s2Ku70₂). We examined the transfection efficiency of binary Ku70₂-NLS/DNA and ternary Ku70₂-NLS/PEI/DNA gene vector complexes in vitro by using standard transfection protocols as well as the magnetofection method. The application of Ku70₂-NLS and s1Ku70₂-NLS increased gene transfer efficiency in vitro and in vivo. This study shows for the first time that the use of bipartite NLS compounds alone or in combination with cationic polymers is a promising strategy to enhance the efficiency of non-viral gene transfer. More...