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CleverGenes SIGNED

Novel Gene Therapy Based on the Activation of Endogenous Genes for the Treatment of Ischemia - Concepts of endogenetherapy, release of promoter pausing, promoter-targeted ncRNAs and nuclear RNAi

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EC-Contrib. €

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 CleverGenes project word cloud

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

diseases    tissues    pigs    vegf    splicing    minimally    chromosomal    applicable    metabolites    successful    self    harbor    angiogenic    severe    ultrasound    upregulation    formed    superenhancerrnas    vectors    crispr    invasive    endogenetherapy    gene    exogenous    patients    integration    imaging    native    clinically    molecules    cdna    outcomes    emphasis    mri    shift    construct    promoter    era    regulated    sites    release    metabolic    lasting    oligonucleotides    myocardial    natural    endogenous    medicine    clusters    therapeutic    clinical    background    pausing    mice    treatment    reversible    circularrnas    transcription    ischemia    activating    photoacoustic    promoters    instead    safe    blood    tissue    programs    introns    vascular    functional    model    begin    lack    paradigm    advancing    epigenetic    vp16    grnamutatedcas9    genomic    significance    transfer    biomedical    centers    newly    small    pet    cardiac    chronic    activate    cardiovascular    flow    rnai    hairpinrnas    genes    nuclear    vegfs    therapy    preclinical    special    endothelial    angiogenesis    clear    platform    exons    upregulating    regions   

Project "CleverGenes" data sheet

The following table provides information about the project.

Coordinator
ITA-SUOMEN YLIOPISTO 

Organization address
address: YLIOPISTONRANTA 1 E
city: KUOPIO
postcode: 70211
website: www.uef.fi

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 Finland [FI]
 Project website http://www.uef.fi/en/web/aivi/seppo-ylaherttuala-group
 Total cost 2˙437˙500 €
 EC max contribution 2˙437˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2020-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ITA-SUOMEN YLIOPISTO FI (KUOPIO) coordinator 2˙437˙500.00

Map

 Project objective

Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.

 Publications

year authors and title journal last update
List of publications.
2017 Seppo Ylä-Herttuala, Andrew H. Baker
Cardiovascular Gene Therapy: Past, Present, and Future
published pages: 1095-1106, ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2017.03.027
Molecular Therapy 25/5 2019-07-05
2017 Johanna Lähteenvuo, Seppo Ylä-Herttuala
Advances and Challenges in Cardiovascular Gene Therapy
published pages: 1024-1032, ISSN: 1043-0342, DOI: 10.1089/hum.2017.129
Human Gene Therapy 28/11 2019-07-05
2012 Nihay Laham-Karam, Pia Laitinen, Tiia A. Turunen, Seppo Ylä-Herttuala
Activating the Chromatin by Noncoding RNAs
published pages: , ISSN: 1523-0864, DOI: 10.1089/ars.2017.7248
Antioxidants & Redox Signaling 2019-07-05
2017 Minna U. Kaikkonen, Paavo Halonen, Oscar Hsin-Fu Liu, Tiia A. Turunen, Juho Pajula, Pierre Moreau, Ilakya Selvarajan, Tomi Tuomainen, Einari Aavik, Pasi Tavi, Seppo Ylä-Herttuala
Genome-Wide Dynamics of Nascent Noncoding RNA Transcription in Porcine Heart After Myocardial InfarctionCLINICAL PERSPECTIVE
published pages: e001702, ISSN: 1942-3268, DOI: 10.1161/CIRCGENETICS.117.001702
Circulation: Cardiovascular Genetics 10/3 2019-07-05
2016 Iiro Hassinen, Antti Kivelä, Antti Hedman, Antti Saraste, Juhani Knuuti, Juha Hartikainen, Seppo Ylä-Herttuala
Intramyocardial Gene Therapy Directed to Hibernating Heart Muscle Using a Combination of Electromechanical Mapping and Positron Emission Tomography
published pages: 830-834, ISSN: 1043-0342, DOI: 10.1089/hum.2016.131
Human Gene Therapy 27/10 2019-07-05
2017 Henri Niskanen, Irina Tuszynska, Rafal Zaborowski, Merja Heinäniemi, Seppo Ylä-Herttuala, Bartek Wilczynski, Minna U Kaikkonen
Endothelial cell differentiation is encompassed by changes in long range interactions between inactive chromatin regions
published pages: 1724-1740, ISSN: 0305-1048, DOI: 10.1093/nar/gkx1214
Nucleic Acids Research 46/4 2019-04-18
2017 Johanna P. Laakkonen, Jari P. Lappalainen, Thomas L. Theelen, Pyry I. Toivanen, Tiina Nieminen, Suvi Jauhiainen, Minna U. Kaikkonen, Judith C. Sluimer, Seppo Ylä-Herttuala
Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling, transcription factor SNAI2 and interleukin-8
published pages: 109-124, ISSN: 0969-6970, DOI: 10.1007/s10456-016-9532-7
Angiogenesis 20/1 2019-04-18
2016 Jussi Nurro, Paavo J Halonen, Antti Kuivanen, Miikka Tarkia, Antti Saraste, Krista Honkonen, Johanna Lähteenvuo, Tuomas T Rissanen, Juhani Knuuti, Seppo Ylä-Herttuala
AdVEGF-B 186 and AdVEGF-D ΔNΔC induce angiogenesis and increase perfusion in porcine myocardium
published pages: 1716-1720, ISSN: 1355-6037, DOI: 10.1136/heartjnl-2016-309373
Heart 102/21 2019-04-18

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