The design of antisense RNA.

Abstract

Antisense nucleic acids comprise short-chain synthetic oligonucleotides, often oligodeoxyribonucleotides (ODN) of less than approximately 30 nucleotides and substantially longer sequences formed by ribonucleic acids (RNA). Both groups differ with respect to several properties, including their generation, the mode of delivery, and their structure-function relationship. Long-chain antisense RNA transcribed in vitro or endogenously from recombinant genes fold into three-dimensional structures. The pairing reaction with their complementary target strand occurs via largely unknown annealing mechanisms and, depending on the phylogenetic cellular background, in different cellular compartments. The annealing pathway is influenced by a variety of biologic and biochemical parameters that are as yet poorly understood. However, the basal biochemical mechanisms underlying the relationship between RNA structure and efficient annealing could allow one to derive more general rules for the design of in vivo effective antisense RNA in a way that is not dependent on specific cell types. Here, some of the criteria are discussed that are currently thought to have major impact on the design of long-chain antisense RNA.