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

ABSTRACT:

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 (fu) in both mouse and human plasma. To further characterize the interaction between ASOs and plasma proteins, individual binding measurements were taken for five major proteins in human plasma: human

SUBMITTER: Yun C 

PROVIDER: S-EPMC11795045 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature