Nonviral gene delivery: Towards artificial viruses

Several limitations to nonviral gene delivery have been overcome. Small nanometric particles have been obtained by condensation ofDNA with a polymerizable cation followed by DNA template-directed homopolymerization of the vector. Targeting of specific cell types has been achieved by using polyethylenimine (PEI), a cationic polymer, coupled to cell ligands such as galactose or small RGD peptide that allows cell entry by a receptor-mediated endocytosis pathway. Escape of the DNA complexes from the endosomes is favored by the 'proton sponge' effect as a consequence of the high buffering capacity of PEI. The last barrier to gene delivery, i.e. the nuclear membrane, can be crossed at the level of the nuclear pore complexes, by using nuclear localization signal DNA molecule conjugates.