Projects per year
Abstract
Chromatin adopts different configurations that are regulated by reversible covalent modifications, referred to as epigenetic marks. Epigenetic inhibitors have been approved for clinical use to restore epigenetic aberrations that result in silencing of tumor-suppressor genes, oncogene addictions, and enhancement of immune responses. However, these drugs suffer from major limitations, such as a lack of locus selectivity and potential toxicities. Technological advances have opened a new era of precision molecular medicine to reprogram cellular physiology. The locus-specificity of CRISPR/dCas9/12a to manipulate the epigenome is rapidly becoming a highly promising strategy for personalized medicine. This review focuses on new state-of-the-art epigenome editing approaches to modify the epigenome of neoplasms and other disease models towards a more 'normal-like state', having characteristics of normal tissue counterparts. We highlight biomolecular engineering methodologies to assemble, regulate, and deliver multiple epigenetic effectors that maximize the longevity of the therapeutic effect, and we discuss limitations of the platforms such as targeting efficiency and intracellular delivery for future clinical applications.
Original language | English |
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Pages (from-to) | 12453-12482 |
Number of pages | 30 |
Journal | Nucleic Acids Research |
Volume | 48 |
Issue number | 22 |
DOIs | |
Publication status | Published - 16 Dec 2020 |
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Reprogramming anti-tumour therapy responses by locus selective manipulation of the epigenome in breast cancer
Blancafort, P., Dolcetti, R., Mazzieri, R., Gaudieri, S. & Norret, M.
National Health & Medical Research Council NHMRC
1/01/20 → 31/12/24
Project: Research
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Targeted epigenetic reactivation of dormant tumor suppressors: New precision therapies for liver cancer
Blancafort, P., Swaminatha Iyer, K., Yeoh, G. & Cursons, J.
National Health & Medical Research Council NHMRC
1/01/19 → 31/12/22
Project: Research
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Reversing epithelial to mesenchymal transition by targeted epigenetic editing in breast cancer
Blancafort, P., Gersbach, C., Thompson, E., Swaminatha Iyer, K., Rots, M., Redfern, A., Chaffer, C. & Cursons, J.
National Health & Medical Research Council NHMRC
1/01/18 → 31/12/22
Project: Research