Dialysis TransplantationEditorial Comments Molecular intervention with antisense oligodeoxynucleotides (ODNs) in nephrology

Manipulation of the expression of a specific gene may the encoded protein. The concentration of RNase H in the nucleus is thought to be higher than that in theshed light on the function of the encoded protein under physiological and pathophysiological conditions as cytoplasm because the enzyme participates in DNA replication. Therefore, intranuclear delivery of anti-well as may form the basis for fundamental therapy of genetic disorders. Among various strategies for gene sense ODNs is important for effective inhibition of protein synthesis.modulation, antisense oligodeoxynucleotides (ODNs) complementary to a target mRNA represent a new For translation arrest, antisense ODNs have been designed to bind to the translational initiation codon.paradigm for drug discovery [1–3]. Thus, antisense ODNs containing 15–30 residues offer the potential to However, targeting the initiation codon does not always result in maximal inhibition of gene expression;block the expression of the corresponding gene. Although unmodified phosphodiester ODNs are antisense ODNs specific for the 3 ∞ non-coding region of mRNAs often provide the greatest inhibition ofrapidly degraded by nucleases, chemical modification can increase their stability and potency. The most protein synthesis [5]. However, non-specific effects of ODNs should bewidely used analogues to date are the phosphorothioate ODNs (S-oligo), in which one of the non-bridging taken into consideration. A sequence-specific action o