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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 €


EC-Contrib. €






 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.

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

Project "R-FunSel" data sheet

The following table provides information about the project.


Organization address
address: STRAND
city: LONDON
postcode: WC2R 2LS

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


Take a look of project's partnership.

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


 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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