chapter  11
17 Pages

Cellular uptake, metabolic stability and nuclear translocation of nucleic acids

ByDELPHINE LECHARDEUR, GERGELY L. LUKACS

INTRODUCTION Genetic material, comprising the information required to maintain the complexity and evolvability of an eukaryotic organism; is largely encoded in the chromosomal DNA and confined to the nucleus. The nuclear envelope and the plasma membrane have an indispensable role in preserving the stability of the nuclear DNA by protecting it from the intrusion of genetic material of pathogenic viruses, bacteria and necrotic or apoptotic cell nuclei. These phospholipid membranes, on the other hand, constitute major obstacles to the nuclear delivery of non-viral vector, which is comprised of an expression cassette, encoded by a therapeutic gene complexed with cationic polymer (polyplex), cationic lipid (lipoplex) or a mixture of these (lipopolyplex). Although the accessibility and specific characteristics of the target organ may impose additional impediments to gene delivery leading to a further decrease in the gene transfer efficiency in vivo, both toxicological and immunological considerations favor the application of synthetic vectors over viral delivery systems to alleviate the phenotypic manifestations of genetic or acquired diseases.