Project description
Gene therapy for an inherited blindness disorder
The blindness disorder retinitis pigmentosa (adRP) is caused by autosomal dominant mutations in RHO, the gene that encodes the rhodopsin protein responsible for converting light into neuronal signals. The EU-funded inSight project proposes to develop a gene therapy approach that combines silencing of the gain-of-function mutations and the simultaneous replacement with a human wild-type copy of the RHO gene. To achieve this, researchers will employ a specific synthetic transcription factor with a zinc-finger scaffold previously shown to facilitate transcriptional repression. The ultimate goal is to commercialise this therapeutic intervention and bring it to the clinic to effectively cure patients with adRP.
Objective
At present therapies for inherited dominant disorders are not available, thus representing an urgent unmet medical and social need. The ERC Grant ALLELECHOKER enabled the PI to discover three modes to generate transcriptional repression by transcription factors (TFs) based on Zinc-finger scaffold: i- synthetic transcription factor (TF; Mussolino et al., EMBO Mol. Med. 2011 Mar;3(3):118-28; Botta S. et al. Elife. 2016 Mar 14;5), ii- synthetic DNA-binding protein (Botta S. et al. Elife. 2016 Mar 14;5) and iii- the ectopic expression of an endogenous TF (Botta S, et al. JCI Insight. 2017 Dec 21;2(24). Thus, the PI demonstrated that transcriptional repression by TFs embodies a novel therapeutically effective mode to treat the toxic effects of gain-of-function mutations causing incurable inherited dominant disorders. In particular, mutations in the RHODOPSIN gene can cause the blindness disorder autosomal dominant retinitis pigmentosa (adRP). The PI demonstrated safety and efficiency of RHODOPSIN gene transcriptional silencing in pre-clinical animal models by a specific synthetic transcriptional repressor (ZF6-DB) delivered to the retina by an adeno-associated virus (AAV) vector (AAV-ZF6-DB). Furthermore, within the ERC Grant ALLELECHOKER the PI showed that a single AAV vector containing two independent expression cassettes (AAV-ZF6-DB-hRHO), enables balanced silencing of RHODOPSIN by ZF6-DB and its simultaneous replacement with a human wild-type copy of the RHODOPSIN gene. The primary objective of the inSight ERC-PoC grant is to support AAV-ZF6-DB-hRHO clinical translation, with the final goal of bringing this therapeutic to patients suffering adRP through market authorization and commercialization.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine ophthalmology
- natural sciences biological sciences genetics mutation
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-POC - Proof of Concept Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-PoC
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80138 Napoli
Italy
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