Baculoviral IAP repeat-containing protein 5 (Survivin) promoter-regulated viral replication (BIRC5-regulated viral replication)

Baculoviral IAP repeat-containing protein 5 (Survivin) promoter-regulated viral replication is a precision oncology strategy that utilizes the tumor-specific activity of the BIRC5 promoter to drive the replication of oncolytic viruses (PubMed: 17545525). BIRC5, a member of the inhibitor of apoptosis (IAP) family, is highly expressed in nearly all human malignancies but is virtually undetectable in most normal adult tissues, providing a high therapeutic index for transcriptional targeting (UniProt: O15392; PubMed: 25605117). In this system, essential viral genes, such as the adenovirus E1A gene, are placed under the transcriptional control of the BIRC5 promoter, ensuring that viral replication and subsequent cell lysis (oncolysis) occur predominantly within malignant cells (PubMed: 18413138). This method aims to enhance the safety profile of oncolytic viruses by minimizing damage to healthy tissues while maintaining potent anti-tumor activity. Clinical and preclinical candidates, such as CRAd-S-pk7, have been developed to treat aggressive cancers like glioblastoma by leveraging this mechanism (ClinicalTrials.gov: NCT03072134). Challenges associated with this target include the potential for "leaky" expression in normal stem cell populations and the host's immune response against the viral vector, which can limit efficacy.

Other names

Survivin promoter-driven oncolytic adenovirusBIRC5-driven oncolytic therapySurvivin-responsive viral replicationTranscriptional targeting of Survivin

Transcriptional targeting where viral replication is restricted to cancer cells overexpressing BIRC5 (Survivin) by placing essential viral genes under the control of the BIRC5 promoter (PubMed: 17545525).