Editorial [Hot Topic: Topical Non-Invasive Delivery Technologies for the Delivery of Genetic Material (Guest Editor: Marianna Foldvari)]

The knowledge of the genome and proteome will result in enormous opportunities in the identification of new therapeutic molecules which will ultimately have a major impact on human health. The new types of pharmaceuticals will be DNA and RNA pieces, small peptides, large proteins and recombinant or subunit vaccines. The science and technology of the delivery and targeting of the 'products' of the genome and proteome are the next crucial links in the development of new approaches for the treatment and prevention of diseases. Developing non-invasive delivery approaches for macromolecules in general is a major challenge. This is conspicuously reflected in the articles in this issue dealing with DNA delivery methods. To replace direct injection using needles or reimplanting ex vivo transfected keratinocytes or dermal fibroblasts, novel delivery methods for oligo- and polynucleotides may include less invasive procedures such as microprojectile techniques, electroporation and topically applied formulations. There is also effort to develop non-viral delivery systems in order to avoid the many disadvantages of viral vectors. This issue of Current Drug Delivery contains a collection of articles focusing on non-invasive delivery of DNA for therapeutic and vaccine purposes. The reviews by von drunen Littel-van den Hurk, Foldvari et al., Cui et al. and Choi and Maibach in this issue provide extensive coverage of the various administration methods of DNA into the body, the differences between the requirements for therapeutic and vaccine DNA and the effect of formulation design on DNA delivery. There are specific examples for dermal, oral, pulmonary and electrically-assisted delivery technologies (Lisziewicz et al., Wang et al., Densmore, Cemazar et al. and Foldvari et al.). There are reports on several novel technologies for non-invasive DNA delivery: silicon microneedles, DNAnanoparticles, biphasic vesicles (Biphasix(™)) and an invasin-based gene targeting system. Birchall et al. demonstrated the ability of microfabricated silicon microneedle arrays to create micron-sized channels through the stratum corneum of excised human skin and the resulting ability of the conduits to facilitate localized delivery of charged macromolecules and plasmid DNA. Lisziewicz et al. have developed a non-viral delivery system where the plasmid DNA, encoding appropriate retroviral genes, is encapsulated within pathogenlike nanoparticles. Topical application of these nanoparticles on abraded skin resulted in suppressed viral replication and increased survival time in HIV-infected macaques. Foldvari et al. demonstrated high level of plasmid DNA delivery after topical application on intact human skin using biphasic vesicles and evaluated the quantitative aspects of DNA delivery. Wang et al. described a Yersinia protein, invasin, that binds to a subset of b1 integrin receptors located on the apical membrane of intestinal M-cells, as potential delivery/targeting agents. By coupling invasin to a micro/nanoparticle carrier, the natural transport mechanism can be utilized for the oral delivery of therapeutic genes and gene-based vaccines. This issue intends to give the readers an excellent overview on issues associated with non-invasive delivery of DNA and some recent developments on potential technologies. It is also intended to reflect on the necessity of further significant efforts into delivery system development for macromolecular therapeutics. Even though the pharmaceutics and the engineering of delivery technologies does not seem (to some) as dazzling as the sequencing of the genome or the compiling of the proteome, it is probably the most crucial task necessary for turning genes and proteins into therapeutic products for humans and animals.