*2.2. Transcriptional and Post-Transcriptional Retargeting Strategies*

Additional strategies to attain cancer specificity and preserve viral virulence include transcriptional retargeting—i.e., placing a critical viral gene under the control of a cancerspecific promoter, post-transcriptional retargeting and combinations thereof [39]. Examples include the control of the key γ34.5 virulence gene by a hybrid nestin enhancer-HSP68 minimal promoter which ensures expression of the HSV genome specifically in the nestinpositive glioblastoma cells [40] and the insertion of miRNA target sequences specific for selected tissues (e.g., brain, heart, or liver) to avoid off-tumor expression of key herpesviral proteins like ICP4 (infected cell protein 4), ICP27, UL8, and γ34.5 [20]. Such approaches have been elegantly reviewed recently [23] and are beyond the scope of current review.
