Disrupting viral autorepression to treat infection

Disrupting viral autorepression with nucleotide decoys that mimic viral cis-regulatory binding sites, but don't activate DNA sensing immune pathways, could help treat viral infections with a high barrier to resistance by causing accumulation of viral transcription factors that promote host cell death.

In a human retinal cell line infected with CMV, a 28bp DNA duplex that acts as a decoy for the beta-herpesvirus immediate early locus and binds its cis-regulatory protein IE86 increased apoptosis and decreased viral titers with an IC50 of 0.95 nM, compared with an IC50 of 30 nM for Vitravene fomivirsen, an antisense oligonucleotide targeting CMV IE2 mRNA. In continuous cultures in which the supernatant from infected cells was added to naive cells every four days, the virus remained undetectable at 52 days in cells treated with the DNA decoy prior to infection, compared with emergence of resistance at 16 days in cells treated with the antiviral fomivirsen. ...