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Angelo Lombardo, M.Sc., Ph.D. - "Targeted Epigenome Editing for Therapeutic and Basic Applications"

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy
When Jun 06, 2017
from 12:00 PM to 01:30 PM
Where tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Abstract
Gene silencing by RNAi and artificial nucleases is a powerful approach to interrogate gene function and holds great therapeutic promise for several diseases. We have developed a novel modality of gene silencing that exploits endogenous epigenetic mechanisms of embryonic stem cells to convey robust and inheritable states of transcriptional repression at the desired target gene in somatic cells. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the desired target locus to instruct de novo DNA methylation. Silencing was sharply confined to the targeted gene, was resistant to exogenous activation and could be relieved by targeted DNA demethylation. We demonstrated the portability of this technology by silencing three highly transcribed genes and using multiple DNA binding platforms. Finally, we expanded the breadth of targeted epigenome editing by multiplex gene silencing within the same cell. Overall, our hit-and-run strategy may provide a powerful new alternative to conventional gene silencing for the treatment of several diseases.

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