Gene Therapy for the Heart Lessons Learned and Future Perspectives

Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells

(2020) Tea Kocijan et al.   CARDIOVASCULAR RESEARCH

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy

(2020) A. Moretti et al.   NATURE MEDICINE

Non-coding RNA therapeutics for cardiac regeneration

(2020) Luca Braga et al.   CARDIOVASCULAR RESEARCH

Cardiac-directed Expression of Adenylyl Cyclase Catalytic Domain (C1C2) Attenuates Deleterious Effects of Pressure Overload

(2019) Zhen Tan et al.   HUMAN GENE THERAPY

Long Non-coding RNAs: At the Heart of Cardiac Dysfunction?

(2019) Lisa Hobuß et al.   Frontiers in Physiology

Next-generation muscle-directed gene therapy by in silico vector design

(2019) S. Sarcar et al.   Nature Communications

SDF-1 plasmid treatment for patients with peripheral artery disease (STOP-PAD): Randomized, double-blind, placebo-controlled clinical trial

(2019) Mehdi H Shishehbor et al.   VASCULAR MEDICINE

Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury

(2019) Austin Borden et al.   CIRCULATION RESEARCH

Therapeutic potential of AAV9-S15D-RLC gene delivery in humanized MYL2 mouse model of HCM

(2019) Sunil Yadav et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs

(2019) Khatia Gabisonia et al.   NATURE

Next-generation AAV vectors - don't judge a virus (only) by its cover

(2019) Claire Domenger et al.   HUMAN MOLECULAR GENETICS

Gene Therapy

(2019) Katherine A. High et al.   NEW ENGLAND JOURNAL OF MEDICINE

Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction

(2019) Feng Gao et al.   Nature Communications

The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy

(2019) Nicolò Salvarani et al.   Nature Communications

Safety Considerations in the Development of Hippo Pathway Inhibitors in Cancers

(2019) Satoko Kakiuchi-Kiyota et al.   Frontiers in Cell and Developmental Biology

Nanoscale delivery systems for microRNAs in cancer therapy

(2019) Sanda Boca et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Gene therapy for atrial fibrillation - How close to clinical implementation?

(2019) Amar Trivedi et al.   INTERNATIONAL JOURNAL OF CARDIOLOGY

Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening

(2018) Oana Sorop et al.   CARDIOVASCULAR RESEARCH

Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration

(2018) Tamer M.A. Mohamed et al.   CELL

Functional Classification and Experimental Dissection of Long Noncoding RNAs

(2018) Florian Kopp et al.   CELL

RNA Therapeutics in Cardiovascular Disease

(2018) Tina Lucas et al.   CIRCULATION RESEARCH

Safety and Efficacy of Adenovirus Carrying Hepatocyte Growth Factor Gene by Percutaneous Endocardial Injection for Treating Post-infarct Heart Failure: A Phase IIa Clinical Trial

(2018) Haoyu Meng et al.   CURRENT GENE THERAPY

Hepatocyte Growth Factor Gene Therapy for Ischemic Diseases

(2018) Li-Sheng Wang et al.   HUMAN GENE THERAPY

Cardiac-Specific Expression of ΔH2-R15 Mini-Dystrophin Normalized All Electrocardiogram Abnormalities and the End-Diastolic Volume in a 23-Month-Old Mouse Model of Duchenne Dilated Cardiomyopathy

(2018) Nalinda B. Wasala et al.   HUMAN GENE THERAPY

Therapeutic approaches for cardiac regeneration and repair

(2018) Hisayuki Hashimoto et al.   Nature Reviews Cardiology

Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis

(2018) David Adams et al.   NEW ENGLAND JOURNAL OF MEDICINE

Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility

(2018) Jayesh A. Kulkarni et al.   Nucleic Acid Therapeutics

miRNAs that Induce Human Cardiomyocyte Proliferation Converge on the Hippo Pathway

(2018) Marta Diez-Cuñado et al.   Cell Reports

Gene Therapy via Trans -Splicing for LMNA -Related Congenital Muscular Dystrophy

(2018) Feriel Azibani et al.   Molecular Therapy-Nucleic Acids

RNA therapeutics for heart disease

(2018) Federica De Majo et al.   BIOCHEMICAL PHARMACOLOGY

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

(2018) Leonela Amoasii et al.   SCIENCE

Inhibition of GSK-3 to induce cardiomyocyte proliferation-a recipe for in situ cardiac regeneration

(2018) Anand Prakash Singh et al.   CARDIOVASCULAR RESEARCH

Adenoviral intramyocardial VEGF-DΔNΔC gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up

(2017) Juha Hartikainen et al.   EUROPEAN HEART JOURNAL

Effect of intracoronary administration of AAV1/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial

(2017) Jean-Sébastien Hulot et al.   EUROPEAN JOURNAL OF HEART FAILURE

Extracellular vesicles for nucleic acid delivery: progress and prospects for safe RNA-based gene therapy

(2017) L Jiang et al.   GENE THERAPY

Small But Increasingly Mighty: Latest Advances in AAV Vector Research, Design, and Evolution

(2017) Dirk Grimm et al.   HUMAN GENE THERAPY

Diabetes Mellitus–Induced Microvascular Destabilization in the Myocardium

(2017) Rabea Hinkel et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure

(2017) Shin Watanabe et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Heart failure

(2017) Marco Metra et al.   LANCET

Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study

(2017) Nico van Zandwijk et al.   LANCET ONCOLOGY

FDA-Approved Oligonucleotide Therapies in 2017

(2017) Cy A. Stein et al.   MOLECULAR THERAPY

Hippo pathway deficiency reverses systolic heart failure after infarction

(2017) John P. Leach et al.   NATURE

The extracellular matrix protein agrin promotes heart regeneration in mice

(2017) Elad Bassat et al.   NATURE

Correction of a pathogenic gene mutation in human embryos

(2017) Hong Ma et al.   NATURE

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

(2017) Kausik K. Ray et al.   NEW ENGLAND JOURNAL OF MEDICINE

Current state of the art for cardiac arrhythmia gene therapy

(2017) J. Kevin Donahue   PHARMACOLOGY & THERAPEUTICS

Cardiac regeneration strategies: Staying young at heart

(2017) Eldad Tzahor et al.   SCIENCE

The long noncoding RNA Wisper controls cardiac fibrosis and remodeling

(2017) Rudi Micheletti et al.   Science Translational Medicine

Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart

(2016) Lingjuan He et al.   CARDIOVASCULAR RESEARCH

Gene transfer to promote cardiac regeneration

(2016) Chiara Collesi et al.   CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES

Mechanisms of Cardiac Regeneration

(2016) Aysu Uygur et al.   DEVELOPMENTAL CELL

Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors

(2016) Muhammad S. Beg et al.   INVESTIGATIONAL NEW DRUGS

Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial

(2016) Barry Greenberg et al.   LANCET

Non-coding RNAs as drug targets

(2016) Masayuki Matsui et al.   NATURE REVIEWS DRUG DISCOVERY

Long noncoding RNA Chast promotes cardiac remodeling

(2016) Janika Viereck et al.   Science Translational Medicine

Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure

(2016) H. Kirk Hammond et al.   JAMA Cardiology

MicroRNA-34a Plays a Key Role in Cardiac Repair and Regeneration Following Myocardial InfarctionNovelty and Significance

(2015) Yanfei Yang et al.   CIRCULATION RESEARCH

Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy

(2015) M. Gramlich et al.   EMBO Molecular Medicine

Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial

(2015) Eugene S. Chung et al.   EUROPEAN HEART JOURNAL

Intracoronary Cytoprotective Gene Therapy

(2015) Felix Woitek et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation

(2015) Gabriele D’Uva et al.   NATURE CELL BIOLOGY

Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

(2015) João Conde et al.   NATURE MATERIALS

Gene therapy to treat cardiac arrhythmias

(2015) Rossana Bongianino et al.   Nature Reviews Cardiology

A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9

(2015) Kelli J. Carroll et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice

(2015) Ying Tian et al.   Science Translational Medicine

Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy

(2015) Ioannis Karakikes et al.   Nature Communications

Extra- and intracellular factors regulating cardiomyocyte proliferation in postnatal life

(2014) S. Zacchigna et al.   CARDIOVASCULAR RESEARCH

In Vivo Activation of a Conserved MicroRNA Program Induces Mammalian Heart Regeneration

(2014) Aitor Aguirre et al.   Cell Stem Cell

Single Delivery of an Adeno-Associated Viral Construct to Transfer the CASQ2 Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age

(2014) Marco Denegri et al.   CIRCULATION

Epigenetic Modification at Notch Responsive Promoters Blunts Efficacy of Inducing Notch Pathway Reactivation After Myocardial Infarction

(2014) Giulia Felician et al.   CIRCULATION RESEARCH

Adeno-Associated Virus Vectors as Therapeutic and Investigational Tools in the Cardiovascular System

(2014) Serena Zacchigna et al.   CIRCULATION RESEARCH

Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model

(2014) Zhiqiang Lin et al.   CIRCULATION RESEARCH

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

(2014) Kiyotake Ishikawa et al.   MOLECULAR THERAPY

Inhibition of miR-25 improves cardiac contractility in the failing heart

(2014) Christine Wahlquist et al.   NATURE

MicroRNAs in myocardial infarction

(2014) Reinier A. Boon et al.   Nature Reviews Cardiology

MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

(2014) Rabea Hinkel et al.   Nature Communications

Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice

(2014) Giulia Mearini et al.   Nature Communications

Single Intracoronary Injection of Encapsulated Antagomir‐92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling

(2014) Neus Bellera et al.   Journal of the American Heart Association

Immune responses to AAV vectors: overcoming barriers to successful gene therapy

(2013) F. Mingozzi et al.   BLOOD

Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model

(2013) Rabea Hinkel et al.   CIRCULATION

An Open-Label Dose Escalation Study to Evaluate the Safety of Administration of Nonviral Stromal Cell-Derived Factor-1 Plasmid to Treat Symptomatic Ischemic Heart Failure

(2013) Marc S. Penn et al.   CIRCULATION RESEARCH

mir-17–92 Cluster Is Required for and Sufficient to Induce Cardiomyocyte Proliferation in Postnatal and Adult Hearts

(2013) Jinghai Chen et al.   CIRCULATION RESEARCH

microRNAs in cardiac development and regeneration

(2013) Enzo R. Porrello   CLINICAL SCIENCE

Hippo signaling impedes adult heart regeneration

(2013) T. Heallen et al.   DEVELOPMENT

Evaluation of ASPIRE trial: a Phase III pivotal registration trial, using intracoronary administration of Generx (Ad5FGF4) to treat patients with recurrent angina pectoris

(2013) Juan Carlos Kaski et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy

(2013) Julie Halkein et al.   JOURNAL OF CLINICAL INVESTIGATION

MicroRNA-34a regulates cardiac ageing and function

(2013) Reinier A. Boon et al.   NATURE

Hippo pathway effector Yap promotes cardiac regeneration

(2013) Mei Xin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys

(2013) F. Mingozzi et al.   Science Translational Medicine

Percutaneous Approaches for Efficient Cardiac Gene Delivery

(2013) Kiyotake Ishikawa et al.   Journal of Cardiovascular Translational Research

Long‐Term miR‐669a Therapy Alleviates Chronic Dilated Cardiomyopathy in Dystrophic Mice

(2013) Mattia Quattrocelli et al.   Journal of the American Heart Association

Safety of Direct Cardiac Administration of AdVEGF-All6A+, a Replication-Deficient Adenovirus Vector cDNA/Genomic Hybrid Expressing All Three Major Isoforms of Human Vascular Endothelial Growth Factor, to the Ischemic Myocardium of Rats

(2013) Stephen M. Kaminsky et al.   Human Gene Therapy Clinical Development

Modulation of Cardiac Contractility by the Phopholamban/SERCA2a Regulatome

(2012) Evangelia G. Kranias et al.   CIRCULATION RESEARCH

AAV9.I-1c Delivered via Direct Coronary Infusion in a Porcine Model of Heart Failure Improves Contractility and Mitigates Adverse Remodeling

(2012) Kenneth M. Fish et al.   Circulation-Heart Failure

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

(2012) M Giacca et al.   GENE THERAPY

SDF-1 in myocardial repair

(2012) M S Penn et al.   GENE THERAPY

Functional screening identifies miRNAs inducing cardiac regeneration

(2012) Ana Eulalio et al.   NATURE

MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles

(2012) Eva van Rooij et al.   NATURE REVIEWS DRUG DISCOVERY

Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

(2012) E. R. Porrello et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy

(2012) Ahmet Ucar et al.   Nature Communications

Current Stem Cell Delivery Methods for Myocardial Repair

(2012) Calvin C. Sheng et al.   Biomed Research International

Intramyocardial plasmid-encoding human vascular endothelial growth factor A165/basic fibroblast growth factor therapy using percutaneous transcatheter approach in patients with refractory coronary artery disease (VIF-CAD)

(2011) Krzysztof Kukuła et al.   AMERICAN HEART JOURNAL

MicroRNA-24 Regulates Vascularity After Myocardial Infarction

(2011) Jan Fiedler et al.   CIRCULATION

Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID)

(2011) Mariell Jessup et al.   CIRCULATION

Effect of Hypoxia-Inducible Factor-1α Gene Therapy on Walking Performance in Patients With Intermittent Claudication

(2011) Mark A. Creager et al.   CIRCULATION

miR-15 Family Regulates Postnatal Mitotic Arrest of Cardiomyocytes

(2011) Enzo R. Porrello et al.   CIRCULATION RESEARCH

Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

(2011) Thomas G. Hullinger et al.   CIRCULATION RESEARCH

Minicells: Versatile vectors for targeted drug or si/shRNA cancer therapy

(2011) Jennifer A MacDiarmid et al.   CURRENT OPINION IN BIOTECHNOLOGY

Novel random peptide libraries displayed on AAV serotype 9 for selection of endothelial cell-directed gene transfer vectors

(2011) K Varadi et al.   GENE THERAPY

Chemical modification and design of anti-miRNA oligonucleotides

(2011) K A Lennox et al.   GENE THERAPY

10-year safety follow-up in patients with local VEGF gene transfer to ischemic lower limb

(2011) K Muona et al.   GENE THERAPY

Long-term VEGF-A expression promotes aberrant angiogenesis and fibrosis in skeletal muscle

(2011) H Karvinen et al.   GENE THERAPY

Knockdown of Cyclin-dependent Kinase Inhibitors Induces Cardiomyocyte Re-entry in the Cell Cycle

(2011) Valeria Di Stefano et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cardiac AAV9-S100A1 Gene Therapy Rescues Post-Ischemic Heart Failure in a Preclinical Large Animal Model

(2011) S. T. Pleger et al.   Science Translational Medicine

A randomised, double-blind, placebo-controlled, multicentre study of the safety and efficacy of BIOBYPASS (AdGVVEGF121.10NH) gene therapy in patients with refractory advanced coronary artery disease: the NOVA trial

(2011) Jens Kastrup et al.   EuroIntervention

Myocardial Transfection of Hypoxia Inducible Factor-1α via an Adenoviral Vector During Coronary Artery Bypass Grafting

(2010) Eckehard Gerd Kilian et al.   CIRCULATION JOURNAL

Intramyocardial VEGF-B 167 Gene Delivery Delays the Progression Towards Congestive Failure in Dogs With Pacing-Induced Dilated Cardiomyopathy

(2010) Martino Pepe et al.   CIRCULATION RESEARCH

MicroRNA Regulatory Networks in Cardiovascular Development

(2010) Ning Liu et al.   DEVELOPMENTAL CELL

Recommendations for Successful Training on Methods of Delivery of Biologics for Cardiac Regeneration

(2010) Nabil Dib et al.   JACC-Cardiovascular Interventions

MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling

(2010) Paula A. da Costa Martins et al.   NATURE CELL BIOLOGY

Inducible adeno-associated virus vectors promote functional angiogenesis in adult organisms via regulated vascular endothelial growth factor expression

(2009) Sabrina Tafuro et al.   CARDIOVASCULAR RESEARCH

Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer

(2009) M Hedman et al.   GENE THERAPY

Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID Trial), a First-in-Human Phase 1/2 Clinical Trial

(2009) Brian E. Jaski et al.   JOURNAL OF CARDIAC FAILURE

Filling the gap in LNA antisense oligo gapmers: the effects of unlocked nucleic acid (UNA) and 4′-C-hydroxymethyl-DNA modifications on RNase H recruitment and efficacy of an LNA gapmer

(2009) Kees Fluiter et al.   Molecular BioSystems

VEGF Gene Therapy Fails to Improve Perfusion of Ischemic Myocardium in Patients With Advanced Coronary Disease: Results of the NORTHERN Trial

(2009) Duncan J Stewart et al.   MOLECULAR THERAPY

MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice

(2009) A. Bonauer et al.   SCIENCE

Evaluation of proinflammatory cytokine production and liver injury induced by plasmid DNA/cationic liposome complexes with various mixing ratios in mice

(2008) Yoshitaka Ito et al.   EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

Polymersome carriers: From self-assembly to siRNA and protein therapeutics

(2008) David A. Christian et al.   EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

Notch activates cell cycle reentry and progression in quiescent cardiomyocytes

(2008) Víctor M. Campa et al.   JOURNAL OF CELL BIOLOGY

Notch1 signaling stimulates proliferation of immature cardiomyocytes

(2008) Chiara Collesi et al.   JOURNAL OF CELL BIOLOGY

Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease

(2008) Zhi-Jian Yang et al.   MOLECULAR BIOLOGY REPORTS

MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts

(2008) Thomas Thum et al.   NATURE

LNA-mediated microRNA silencing in non-human primates

(2008) Joacim Elmén et al.   NATURE

Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis

(2008) E. van Rooij et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA