The Paper -> https://www.nature.com/articles/s41467-024-48031-8
While gene editing is currently the major approach used in CRISPR-based therapeutics, epigenetic editing – changing histone modifications, DNA methylation, or gene expression levels without changing genetic sequences – could be a powerful alternative in some diseases.
We collaborated with scientists from Chinese University of Hong Kong, Karolinska Institutet, Jackson Laboratory and Arizona State University, to develop an RNA-lipid nanoparticle (LNP)-delivered epigenetic editing approach for cancer therapy in Epstein-Barr virus (EBV)-associated malignancies.
EBV infection is prevalent across the global population. Latent EBV infection may lead to a variety of malignancies, including nasopharyngeal carcinoma, some forms of gastric cancers and lymphoma, etc. Continued presence of viral genome in latent state in EBV-associated cancer cells represent a unique target for therapeutic interventions. A potential approach to eliminate EBV-associated cancer cells is by activating EBV lytic cycle from latent state to induce growth arrest, apoptosis and cell rupture.
We used CRISPR- and TALE-based activators to turn on lytic genes on EBV genomes within cancer cells. For delivery, we used lipid nanoparticle to encapsulate nucleoside-modified mRNA encoding these synthetic activators and showed potency and safety of these LNPs-delivered activator in suppressing tumor growth in mouse models in vivo. These results demonstrate the potential of epigenetic editing approach for cancer therapeutics.