Characterizing the plasma protein binding profiles of chemistry diversified antisense oligonucleotides in human and mouse plasma using an ultrafiltration method.

Introduction: Plasma protein binding plays a significant role in influencing the pharmacokinetic and pharmacodynamic properties of drugs. This study focuses on examining two pairs of sequence-matched ASOs: phosphorodiamidate morpholino oligomers (PMOs) and 2'-O-methoxyethyl/phosphorothioate (MOE/PS)-modified ASOs, to assess their plasma protein binding profiles.

Methods: The binding of both PMO and MOE/PS-modified ASOs was investigated using an ultrafiltration method combined with hybridization electrochemiluminescence, allowing for the measurement of the unbound fraction (u) in both mouse and human plasma.