Pharmacokinetics and biodistribution of phosphorodiamidate morpholino antisense oligomers

The concept of using antisense oligonucleotides to interfere with gene expression offers a new therapeutic strategy for the treatment of diseases resulting from overexpression or dysfunction of certain genes. Phosphorodiamidate morpholino oligomers (PMOs) represent a neutral class of antisense agents that interfere with target gene expression either by binding and sterically blocking the assembly of translation machinery, resulting in inhibition of translation, or by altering splicing of pre-mRNA. Studies in animal models and human clinical trials have demonstrated a high degree of functional bioavailability in several target organs. Preclinical and clinical studies have shown that PMOs demonstrate improved efficacy, excellent kinetic behavior, biological stability, and a good safety profile. We conclude from the emerging data that PMOs display advantageous pharmaceutical properties in comparison with other antisense strategies.