chapter  19
23 Pages

Basic pharmacokinetics of oligonucleotides and genes

ByMAKIYA NISHIKAWA, YOSHINOBU TAKAKURA, FUMIYOSHI YAMASHITA, MITSURU HASHIDA

INTRODUCTION The ultimate goal of gene therapy is to cure inheritable and acquired diseases in a straightforward manner by correcting abnormalities in genes. Various protocols have been employed to express gene product including the addition of the wild-type gene, correcting mutation in the gene, or suppressing undesirable gene products by blocking mRNA with complementary antisense oligonucleotide. Like conventional drugs and biologically active protein drugs, the administration of plasmid DNA (pDNA) and oligonucleotide (both are called ‘gene drugs’) directly to patients represents an ideal methodology for the treatment of a variety of diseases. Following in vivo administration, however, they encounter many hurdles that must be overcome for a successful therapy.