Progress

Prospects

Mechanisms of nuclear localization signal (NLS)-mediated protein nuclear import have been elucidated. Transcription factor-binding sites promote DNA nuclear translocation. Cell-specific transcription factors drive cell-specific DNA nuclear entry. Proteomics approaches have been used successfully to study DNA nuclear entry. NLS peptides complexed with plasmids may enhance DNA nuclear translocation. Nuclear proteins complexed with plasmids facilitate DNA nuclear entry. Small molecule ligands bound to DNA can increase nuclear entry. Nanoparticles and polymers may provide alternative routes to the nucleus. Modulation of the nuclear pore complex may aid in nuclear delivery of DNA.

Proteomics will blossom in the area of gene delivery. Large-scale identification of proteins in the DNA–protein complex will aid in understanding of how transport occurs. RNA interference will be used increasingly to define key mechanisms of intracellular trafficking of non-viral vectors. Improvements in in vivo imaging on the single cell level will allow the study of intracellular trafficking of plasmids within tissues of living animals. Complexation of proteins with DNA will facilitate general nuclear import and gene expression. Designer proteins containing DNA-binding domains and spatially distinct NLSs may enhance plasmid nuclear import and expression.