CRISPR ENGINEERING STRATEGIES FOR EPIGENETIC REPROGRAMMING IN CANCER THERAPEUTICS

Abstract

Background: Epigenetic dysregulation is a major contributor to cancer initiation, progression, metastasis, and therapeutic resistance through modulation of gene expression without changes in DNA sequences. Aberrant DNA methylation and histone modifications frequently repress tumor suppressor genes and activate oncogenic pathways in cancer cells.

Objective: This study aimed to explore CRISPR engineering strategies for targeted epigenetic reprogramming in cancer therapeutics, utilizing CRISPR-dCas9 mediated epigenome editing systems.

Methodology: Experimental analyses were carried out using human cancer cell lines which were treated with CRISPR-dCas9 systems coupled with epigenetic modifiers like VP64, KRAB, TET1 and p300. Therapeutic efficiency was evaluated by DNA methylation analysis, histone acetylation assessment, quantitative PCR, apoptosis assay and cell proliferation study.

Findings: CRISPR-mediated epigenetic reprogramming restored tumor suppressor gene expression by 68% and reduced oncogenic signaling activity by 54%. Histone acetylation increased by 47% and aberrant DNA methylation levels decreased by 42% in treated cancer cells. Targeted epigenetic modification significantly increased apoptosis rates.

Conclusion: CRISPR-based epigenetic engineering shows great therapeutic potential for precision oncology via targeted gene regulation and epigenetic normalization in cancer cells.