Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice

U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribu...

Full description

Saved in:
Bibliographic Details
Main Authors: Medha Satti, Kavita Prasad, Yash Patel, Demi Poulathas, Lawrence Walker, Esha Paghdal, Samuel Gunderson, Lei Yu
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Research in Pharmacology and Drug Discovery
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590257125000082
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribution after intrathecal drug delivery. We investigated the distribution patterns of U1 Adaptor upon intrathecal bolus administration in mice. It readily distributes to CNS tissues, including the lumbar and the cervical spinal cord, and the cerebellum. Over time, the U1 Adaptor also accumulates in the periphery, both in the liver and the kidneys, while plasma levels are undetectable. Our findings provide useful information for future in-depth pharmacokinetic modeling of U1 Adaptor distribution upon intrathecal administration.
ISSN:2590-2571