chapter  16
32 Pages

Peptide-based gene delivery systems

ByPATRICK MIDOUX, CHANTAL PICHON

INTRODUCTION Gene therapy aims at introducing nucleic acids or genetic material into mammalian cells for the modulation of gene expression with the expectation of getting therapeutic benefits. To date, although viral vectors are the best vehicles to introduce genes into cells and the feasibility of this therapeutic approach has been demonstrated, clinical developments require the use of synthetic vehicles of high safety, low immunogenicity and ease of manufacture. During the last decade, efforts have been made to design peptidebased gene delivery systems that incorporate viral-like features for efficient transfection (Tomlinson and Rolland, 1996; Zauner et al., 1998; Rolland, 1998; Mahato et al., 1999a). By taking advantage of the DNA self-assembling with a cationic polymer to condense a plasmid DNA (pDNA), like the viral genome in the viral particles, polyplexes (DNA/cationic polymer complexes) (Felgner et al., 1997) have been prospected to develop non-viral vectors. The final goal of these systems is to transform the pDNA encoding a therapeutic gene into a ‘Magic Bullet’, as proposed by Paul Erlich (1906), which would be suitable for the delivery of genes into the right target cells and for the translocation to the nucleus of these cells upon systemic administration.