CRISPR-Mediated Cancer Therapies: Approaches to Direct Tumor Targeting - PubMed
4 hours ago
- #Gene Editing
- #CRISPR-Cas9
- #Cancer Therapy
- CRISPR-Cas9 technologies enable precision cancer treatment, overcoming limitations of conventional therapies like chemotherapy and radiation.
- Strategies for direct tumor targeting include oncogene inactivation, tumor suppressor gene reactivation, and tumor microenvironment (TME) modification.
- Key advances involve KRASG12D inactivation via base editing, TP53 correction through homologous recombination, and CDKN2A epigenetic remodeling using CRISPR-dCas9-TET1 demethylation.
- CRISPR screening has identified synthetic lethal interactions, such as PARP1 dependency in BRCA1-/- tumors.
- TME editing strategies, including modification of cancer-associated fibroblasts, enhance antitumor responses.
- Delivery challenges are addressed through viral vectors (adenovirus, AAV, lentivirus) and non-viral approaches (lipid nanoparticles, gold nanoparticles, exosomes, stimuli-responsive systems).
- Clinical trials with CRISPR-engineered T-cells (e.g., CTX130) show remission rates in hematologic malignancies.
- Challenges include cytokine release syndrome, immunotoxicity, tumor heterogeneity, and limited delivery efficiency in solid tumors.
- Overcoming barriers requires interdisciplinary innovation, ethical oversight, and technological refinement for safe and effective integration into precision oncology.