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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.

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

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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