Tissue pharmacokinetics of antisense oligonucleotides.

Pharmacokinetics (PK) of antisense oligonucleotides (ASOs) is characterized by rapid distribution from plasma to tissue and slow terminal plasma elimination driven by re-distribution from tissue. Quantitative understanding of tissue PK and RNA knockdown for various ASO chemistries, conjugations, and administration routes is critical for successful drug discovery. Here, we report concentration-time and RNA knockdown profiles for a gapmer ASO with locked nucleic acid ribose chemistry in mouse liver, kidney, heart, and lung after subcutaneous and intratracheal administration. Additionally, the same ASO with liver targeting conjugation (galactosamine-

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© 2024 The Author(s).

Déclaration de conflit d'intérêts

This study was sponsored by AstraZeneca. All authors were employees of AstraZeneca at the time of this research. P.J. is associate editor at Molecular Therapy Nucleic Acids.