Figure 1 - Nucleic acid–based antiviral strategies.

Antiviral nucleic acids can either be transfected into cells (e.g., siRNA or antisense oligonucleotides) or expressed intracellularly (shRNA, ribozymes or RNA decoys). Viral transcripts complementary to the siRNA/shRNA are cleaved upon assembly of the RISC machinery. RISC is not able to target RNA genomes that are protected within viral capsids or shielded from RNAi attack in subcellular compartments (e.g., the nucleus or virus-induced vesicles). Modified antisense oligonucleotides have a high affinity for their target sequence and inhibit gene expression by steric hindrance of the ribosome, splicing (within the nucleus) or through induction of mRNA cleavage by recruitment of RNase H. Binding of ribozymes to the target sequence should also trigger cleavage of the viral RNA. Decoy RNAs bind and sequester essential viral proteins or host cell factors that support virus replication.