Reducing gene expression in the brain via antisense methods

• Published in: Current protocols in neuroscience Vol. Chapter 5; p. Unit 5.4
• Main Authors: Ouagazzal, A M, Tepper, J M, Creese, I
• Format: Journal Article
• Language: English
• Published: United States 01.05.2001
• Subjects: Animals; Brain Chemistry - genetics; Gene Expression Regulation - physiology; Gene Targeting - methods; Injections, Intraventricular; Male; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - biosynthesis; Oligonucleotides, Antisense - genetics; Rats; Rats, Sprague-Dawley
• ISSN: 1934-8576
• DOI: 10.1002/0471142301.ns0504s00

This unit presents protocols that employ antisense oligodeoxynucleotides to reduce expression of target proteins in the brain. These oligonucleotides are generally designed to inhibit synthesis of a specific protein by hybridization to its mRNA. Because oligonucleotides show very poor penetration into the central nervous system (CNS) after systemic administration, they are either injected into the cerebrospinal fluid (CSF) or infused directly into the brain parenchyma. In this unit, the procedure most commonly used for delivering oligonucleotides continuously into CSF is outlined. In addition, a procedure is described for continuous infusion of oligonucleotides into a specific brain region, using the substantia nigra as an example.