Enhancing Temozolomide (TMZ) chemosensitivity using CRISPR-dCas9-mediated downregulation of O6-methylguanine DNA methyltransferase (MGMT)

May 19, 2024Journal of neuro-oncology

Improving Temozolomide chemotherapy by reducing DNA repair enzyme MGMT using CRISPR-dCas9

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Abstract

A significant reduction in MGMT expression was observed, leading to heightened sensitivity to Temozolomide (TMZ) in the HEK293T cell line.

  • MGMT is associated with resistance to the chemotherapy drug Temozolomide (TMZ) in glioblastoma.
  • Selective downregulation of MGMT transcription was achieved using a CRISPR-based approach combining inactive Cas9 with DNA methyltransferases.
  • Inducing methylation at the MGMT promoter and K-M enhancer resulted in decreased MGMT levels.
  • The enhanced sensitivity to TMZ suggests a potential strategy to overcome drug resistance in glioblastoma cells.

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