Intrathecal Delivery of Therapeutic Oligonucleotides for Potent Modulation of Gene Expression in the Central Nervous System

Zachary Kennedy; James W Gilbert; Bruno M D C Godinho

doi:10.1007/978-1-0716-2010-6_24

Intrathecal Delivery of Therapeutic Oligonucleotides for Potent Modulation of Gene Expression in the Central Nervous System

Methods Mol Biol. 2022:2434:345-353. doi: 10.1007/978-1-0716-2010-6_24.

Authors

Zachary Kennedy^#¹, James W Gilbert¹, Bruno M D C Godinho^#²

Affiliations

¹ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
² RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. [email protected].

^# Contributed equally.

Abstract

Therapeutic oligonucleotides hold tremendous potential for treating central nervous system (CNS) disorders. The route of administration of oligonucleotides significantly impacts both distribution and silencing efficiency. Here, we describe a technically simple, clinically relevant method to administer oligonucleotide compounds into the CNS via direct intrathecal injections. This method achieves distribution throughout the CNS rapidly and permits high-throughput testing of oligonucleotide efficacy and potency in mammals.

Keywords: Antisense oligonucleotides; CNS administration; CSF infusion; Gene silencing; IT dosing; Intrathecal injections; Modified oligonucleotides; Therapeutic oligonucleotides; siRNA.

MeSH terms

Animals
Central Nervous System / metabolism
Gene Expression
Injections, Spinal / methods
Oligonucleotides* / metabolism
Oligonucleotides, Antisense*

Substances

Oligonucleotides
Oligonucleotides, Antisense