Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS


ALLELECHOKER Streszczenie raportu

Project ID: 311682
Źródło dofinansowania: FP7-IDEAS-ERC
Kraj: Italy

Mid-Term Report Summary - ALLELECHOKER (DNA binding proteins for treatment of gain of function mutations)

The Overall objective of the ERC grant is the design and development of DNA-binding molecules to either repress via transcriptional repressors or inactivate via targeted nucleases silencing Rhodopsin (RHO) expression.
This is the first step towards the development of a "mutational-independent" strategy to cure retinitis pigmentosa via the development of a "silencing-replacement" approach.
We proposed three main objectives:
Objective (1) Construction of transcriptional repressors and nucleases for RHO silencing. Objective (2) RHO silencing in photoreceptors. Objective (3) Tuning silencing and replacement.
Objective 1 and 2: as proposed we generated a series of Zinc-figer or transcription activator-like effector (TALE) based repressors and characterized them. Among others the ZF6-DB protein has been showing great therapeutic value and is currently under further characterization for pre-clinical development.
Objective 3: we obtained results supporting the feasibility of silencing and replacement in the context of AAV-vector retinal gene transfer.
We set up the conditions to transduce retinal explants in pigs and currently we are investigating the reliability ex vivo transduction in terms of modeling of the in vivo transduction. This part of the project will be instrumental for the investigation of human post-mortem transduction proposed in the project. We set up a collaboration with “ Fondazione Banca degli Occhi del Veneto – ONLUS” and soon we will able to receive human post-mortem retinal sample to directly assess the efficacy of ZF6-DBD silencing and replacement approach as proposed in the “AlleleChokers” project.

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