SRY-box transcription factor 2 and SRY-box transcription factor 9 (SOX2/SOX9)

The target refers to a specific set of tumor-enriched transcription factors, primarily SRY-box transcription factor 2 (SOX2) and SRY-box transcription factor 9 (SOX9), which are master regulators of the glioblastoma stem cell (GSC) state (Koeber et al., 2026). These factors are highly expressed in aggressive brain tumors and are essential for maintaining the self-renewal and tumorigenic potential of cancer stem cells (oncobriefs.com). In a novel gene therapy approach developed by researchers at the University of Edinburgh and Trogenix, a synthetic super-enhancer (SSE) is engineered to contain clusters of binding sites for these specific transcription factors, allowing for highly selective and potent transgene expression within the tumor microenvironment (allsci.com). This SSE drives the expression of a dual payload: Herpes Simplex Virus thymidine kinase (HSV-TK), which induces cell death upon administration of ganciclovir, and Interleukin-12 (IL-12), which stimulates a localized immune response against the tumor (google.com). The interaction between the tumor's endogenous transcriptional machinery and the synthetic genetic construct (such as TGX-007) enables a search-and-destroy mechanism that targets the most resistant cell populations (oncobriefs.com). This strategy is designed to overcome the heterogeneity of glioblastoma by leveraging the cell's own identity-defining circuitry to trigger its destruction while sparing healthy brain tissue (allsci.com).

Other names

Tumor-enriched transcription factorsGlioblastoma stem cell transcription factorsSOX2SOX9GSC-specific transcription factorsSynthetic super-enhancer binding factors

The synthetic super-enhancer (SSE) is activated by the binding of tumor-enriched transcription factors (SOX2 and SOX9), which recruits the transcriptional machinery to drive the expression of therapeutic payloads HSV-TK and IL-12 specifically in cancer cells.