Our Projects

Our platforM

We discovered a class of specialized RNAs interacting with the mammalian DNMT1 – DNMT1-interacting RNAs (DiRs). DiRs prevent DNA methylation and gene silencing in a locus-specific manner, by binding and inhibiting DNMT1 .

RNA-guided platforms can be used to inhibit DNMT1 and diseases caused by aberrant DNA methylation.

APPLICATIONS

Selective and Gene-specific DNMT inhibitors in multiple disorders

Cancer

Lung (RASSF1;ESR1;MGMT), Breast (BRCA1, CDH1, MGMT, GSTP1, ESR1); Colon (P16;MGMT; GSTP1), Leukemia (P15; DAPK1; CDH1; ESR1), Prostate (GSTP1), Retinoblastoma (RB1) etc.

Genetic Diseases

Fragile X syndrome (FMR1); Myotonic dystrophy (DMPK); Prader Willi Syndrome (IPW); Amyotrophic Lateral Sclerosis (C9orf72); Retinoblastoma (RB); Lynch Syndrome (MLH1/EPM2AIP1) etc

Neurological Disorders

Alzheimer's disease (NEP)

Autoimmune Diseases

Reumathoid arthritis (SAT2; SAT3)

Pipeline

Oncology

MDS

NSCLC

Rare Disease

Fragile X

Metabolic Disorders

Not Disclosed

Our Publications

Di Ruscio, A., A. K. Ebralidze, T. Benoukraf, G. Amabile, L. A. Goff, J. Terragni, M. E. Figueroa, L. L. De Figueiredo Pontes, M. Alberich-Jorda, P. Zhang, M. Wu, F. D’Alo, A. Melnick, G. Leone, K. K. Ebralidze, S. Pradhan, J. L. Rinn and D. G. Tenen (2013). DNMT1-interacting RNAs block gene-specific DNA methylation. Nature

Esposito CL, Autiero I, Sandomenico A, Li H, Bassal MA, Ibba ML, Wang D, Rinaldi L, Ummarino S, Gaggi G, Borchiellini M, Swiderski P, Ruvo M, Catuogno S, Ebralidze AK, Kortylewski M, de Franciscis V, Di Ruscio A (2023). Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation. Nat Comm

Kwon, J., Y. V. Liu, C. Gao, M. A. Bassal, A. I. Jones, J. Yang, Z. Chen, Y. Li, H. Yang, L. Chen, A. Di Ruscio, Y. Tay, L. Chai and D. G. Tenen (2021). Pseudogene-mediated DNA demethylation leads to oncogene activation. Sci Adv

Liu, Y. V., M. A. Bassal, Q. X. X. Lin, C.-S. Wu, J. Kwon, Q. Zhou, H. K. Tan, A. K. Ebralidze, L. Chai, T. Benoukraf, A. Di Ruscio and D. G. Tenen (2020). Targeted intragenic demethylation initiates chromatin rewiring for gene activation. bioRxiv