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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.

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

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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