Fomivirsen

Fomivirsen is a phosphorothioate oligonucleotide that inhibits the replication of human cytomegalovirus (HCMV) through an antisense mechanism. The nucleotide sequence is complementary to a sequence in mRNA transcripts of the major immediate early region 2 (IE2) of human CMV, which encodes several proteins responsible for regulation of viral gene expression that are essential for viral replication. The IE2 gene is essential for early viral gene expression and viral replication; it was shown that the IE2 gene transactivate most human CMV promoters. Protein product from the IE2 region also acts as autorepressor that represses transcription of the IE1 and IE2 genes by binding the cis repression sequence (CRS). It is proposed that the IE2 region interacts with multiple basal and general transcription factors, as well as cell cycle regulators, and it also plays a critical role in controlling the entry of the virus into the lytic cycle from the latent state to further potentiate the infection cascade. Upon binding to the target mRNA, fomivirsen inhibits the IE2 protein synthesis and disrupts viral replication.