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Human cytomegalovirus (HCMV) immediate-early 2 (IE2) mRNA is a critical viral transcript that encodes the IE2 protein, also known as IE86 (Stinski & Isomura, 2008). This protein serves as a master transcriptional regulator essential for the progression of the HCMV life cycle from the immediate-early phase to the early and late phases of viral gene expression (White et al., 2007). By transactivating various viral and cellular promoters, the IE2 protein facilitates efficient viral replication and modulates the host cellular environment to favor viral production. In clinical contexts, HCMV infection can lead to severe complications such as CMV retinitis, particularly in immunocompromised individuals like those with HIV/AIDS (Jabs et al., 2013). The IE2 mRNA became a landmark therapeutic target with the development of Fomivirsen, the first FDA-approved antisense oligonucleotide (Grillone & Lans, 2001). Fomivirsen works by binding to a specific sequence within the IE2 mRNA, thereby blocking its translation and inhibiting the production of the essential IE2 protein, which effectively halts viral replication (Roehr, 1998).
Antisense oligonucleotide-mediated inhibition of translation by complementary binding to the viral mRNA, preventing the synthesis of the IE2 protein (Grillone & Lans, 2001).
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