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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 €

0

EC-Contrib. €

0

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.

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

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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