Nuclear Localisation Sequence Templated Nonviral Gene Delivery Vectors: Investigation of Intracellular Trafficking Events of LMD and LD Vector Systems (pages 286–298)
Michael Keller, Richard P. Harbottle, Eric Perouzel, Morvane Colin, Imran Shah, Ahad Rahim, Laurence Vaysse, Anna Bergau, Sylviane Moritz, Christiane Brahimi-Horn, Charles Coutelle and Andrew D. Miller
Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390049
Shut out by a wall: Transport of exogenous DNA into the nucleus is a prerequisite for successful gene therapy. In vitro, one of the major barriers turns out to be the nuclear membrane, which effectively shields the nucleus from the uptake of exogenous plasmid DNA, as depicted in the figure. The electrostatic complexation of DNA with mu peptide, which harbours a nuclear localisation sequence, is not sufficient to overcome the nuclear barrier. Therefore, for successful gene therapy protocols, strategies must be found to actively promote the uptake of transgenes into the nucleus.