In vivo Pharmacokinetic and Biodistribution profile of Peptide-Conjugated Phosphorodiamidate Morpholino Oligonucleotides

Antisense oligonucleotide (AON) induced exon skipping is one of the most promising strategies for treating Duchene muscular dystrophy (DMD). Morpholino oligos (PMO) and next generation peptide conjugated PMOs (P-PMO) are currently being developed for DMD with encouraging results. Quantitation of oligos in biological samples is required for determining pharmacokinetic (PK) and biodistribution (BD) profile of the drug, which is essential for drug development. We have recently developed an ultrasensitive hybridization-based ELISA method for quantifying PMOs and P-PMOs in biological samples (Burki et al 2015). Initial PK-BD data in mdx mice (mouse model of DMD) suggests P-PMO exhibits a possible 3-compartmental model, which suggests P-PMO is subsequently released from tissue. The data also suggests that P-PMO but not PMO is able to cross the blood brain barrier.