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R-FunSel SIGNED

In vivo functional screening via CRISPR-Cas9 to systematically identify cardiomyocyte receptors as targets for the innovative therapies for myocardial infarction and heart failure

Total Cost €

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EC-Contrib. €

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Partnership

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 R-FunSel project word cloud

Explore the words cloud of the R-FunSel project. It provides you a very rough idea of what is the project "R-FunSel" about.

inserts    identification    systematic    measured    single    desperate    weeks    function    medical    adeno    code    strategy    sequencing    takes    biochemical    quick    individually    unbiased    survival    technologies    editing    first    mouse    vivo    gene    few    stimulus    medicine    frequency    innovative    detrimental    mice    activating    power    infarction    construct    sgrnas    arrayed    cardiotropic    receptor    social    solid    cell    advantage    translational    darwinian    phenotypic    library    vector    basic    protective    sg    cardioprotective    cloned    cardiomyocyte    selective    expressed    screening    form    therapeutics    heart    rnas    burden    recovered    molecules    cardiomyocytes    myocardial    reverse    vectors    named    receptors    transduce    either    worldwide    economic    aav9    intracardiac    lost    driving    druggable    inhibiting    serotype    tissue    functional    multiplicity    enriched    cas9    transgenic    pace    move    ligands    guide    funsel    generation    therapies    feasibility    enters    mi    genes    crispr    pools    virus    genome   

Project "R-FunSel" data sheet

The following table provides information about the project.

Coordinator
KING'S COLLEGE LONDON 

Organization address
address: STRAND
city: LONDON
postcode: WC2R 2LS
website: www.kcl.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 212˙933 €
 EC max contribution 212˙933 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KING'S COLLEGE LONDON UK (LONDON) coordinator 212˙933.00

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 Project objective

Myocardial Infarction (MI) is the leading cause of heart failure, which represents a major medical, social and economic burden worldwide. There is a desperate need for new therapies for these conditions. Here we propose a new approach for the in vivo, unbiased and systematic identification of receptors involved in MI, which might become targets for innovative therapeutics. The method we developed, named Reverse Functional Selection (R-FunSel) takes advantage of the CRISPR/Cas9 genome editing technology and is based on the intracardiac screening of a library of single-guide (sg) RNAs in Cas9 transgenic mice upon gene delivery using the highly cardiotropic adeno-associated virus serotype 9 (AAV9). First, we will construct an arrayed library of sgRNAs, individually cloned into AAV9 vectors, driving CRISPR/Cas9 towards each of the receptor genes expressed by cardiomyocytes. Second, we will package pools of this library and transduce the mouse heart, at a multiplicity by which each vector enters a different cell. Then, MI will be applied as a selective stimulus and, after a few weeks, vector inserts will be recovered from the viable tissue and their frequency measured by Next Generation Sequencing. R-FunSel is based on Darwinian selection of cardiomyocyte survival, thus sgRNAs that will be lost are likely to target cardioprotective genes while those that are enriched code for detrimental factors. The choice to develop R-FunSel for the systematic screening of cardiomyocyte receptors will allow identification of novel druggable targets for the development of therapeutics, either in the form of molecules activating the protective receptors or inhibiting them or their ligands. R-FunSel is based on solid technologies that support the feasibility and power of the in vivo screening approach. Compared to biochemical or phenotypic studies, screening in vivo directly for function is a novel strategy to move basic research into translational medicine at a quick pace.

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