ALLELECHOKER

DNA binding proteins for treatment of gain of function mutations

 Coordinatore FONDAZIONE TELETHON 

Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.

 Nazionalità Coordinatore Italy [IT]
 Totale costo 1˙354˙840 €
 EC contributo 1˙354˙840 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2012-StG_20111109
 Funding Scheme ERC-SG
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-02-01   -   2018-01-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    FONDAZIONE TELETHON

 Organization address address: VIA VARESE 16/B
city: ROMA
postcode: 185

contact info
Titolo: Dr.
Nome: Enrico Maria
Cognome: Surace
Email: send email
Telefono: +39 081 6132334
Fax: +39 081 6132351

IT (ROMA) hostInstitution 1˙354˙840.00
2    FONDAZIONE TELETHON

 Organization address address: VIA VARESE 16/B
city: ROMA
postcode: 185

contact info
Titolo: Mrs.
Nome: Irene
Cognome: Mearelli
Email: send email
Telefono: +39 06 440151
Fax: +39 06 44015521

IT (ROMA) hostInstitution 1˙354˙840.00

Mappa

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 Word cloud

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repression    genome    transcriptional    determine    repressors    gene    human    disease    genomic    nucleases    silencing    zf    rho    photoreceptors    binding    generate    dna    directed    replacement    proteins    strategy    silencers   

 Obiettivo del progetto (Objective)

'Zinc finger (ZF) and transcription activator-like effector (TALE) based technologies are been allowing the tailored design of “artificial” DNA-binding proteins targeted to specific and unique DNA genomic sequences. Coupling DNA binding proteins to effectors domains enables the constitution of DNA binding factors for genomic directed transcriptional modulation or targeted genomic editing. We have demonstrated that pairing a ZF DNA binding protein to the transcriptional repressor Kruppel-associated box enables in vivo, the transcriptional repression of one of the most abundantly expressed gene in mammals, the human rhodopsin gene (RHO). We propose to generate RHO DNA binding silencers (“AlleleChoker”), which inactivate RHO either by transcriptional repression or targeted genome modification, irrespectively to wild-type or mutated alleles (mutational-independent approach), and combine RHO endogenous silencing to RHO replacement (silencing-replacement strategy). With this strategy in principle a single bimodal bio-therapeutic will enable the correction of any photoreceptor disease associated with RHO mutation. Adeno-associated viral (AAV) vector-based delivery will be used for photoreceptors gene transfer. Specifically our objectives are: 1) Construction of transcriptional repressors and nucleases for RHO silencing. Characterization and comparison of RHO silencing mediated by transcriptional repressors (ZFR/ TALER) or nucleases (ZFN/ TALEN) to generate genomic directed inactivation by non-homologous end-joining (NHEJ), and refer these results to RNA interference (RNAi) targeted to RHO; 2) RHO silencing in photoreceptors. to determine genome-wide DNA binding specificity of silencers, chromatin modifications and expression profile on human retinal explants; 3) Tuning silencing and replacement. To determine the impact of gene silencing-replacement strategy on disease progression in animal models of autosomal dominant retinitis pigmentosa (adRP) associated to RHO mutations'

Altri progetti dello stesso programma (FP7-IDEAS-ERC)

REPMIT (2011)

THE ENZYMATIC MACHINERY OF HUMAN MITOCHONDRIAL DNA MAINTENANCE

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LIPS (2011)

Lexical information processes and their spatio-temporal dynamics

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MOLSPINTRON (2012)

Synthetic Expansion of Magnetic Molecules Into Spintronic Devices

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