Towards a new concept of gene inactivation: specific RNA cleavage by endogenous ribonuclease P

Abstract

In the first part of this chapter, general concepts for gene inactivation, antisense techniques and catalytic RNAs (ribozymes) are presented. The requirements for modified oligonucleotides are discussed with their effects on the stability of base-paired hybrids and on resistance against nuclease attack. This also includes the problems in the choice of an optimal target sequence within the inactivated RNA and the options of cellular delivery systems. The second part describes the recently introduced antisense concept based on the ubiquitous cellular enzyme ribonuclease P. This system is unique, since the substrate recognition requires the proper tertiary structure of the cleaved RNA. General properties and possible advantages of this approach are discussed.