Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Delivering efficient liver-directed AAV-mediated gene therapy

(2017) J Baruteau et al.   GENE THERAPY

Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models

(2017) Randy J. Chandler et al.   HUMAN GENE THERAPY

A 5′ Noncoding Exon Containing Engineered Intron Enhances Transgene Expression from Recombinant AAV Vectors in vivo

(2017) Jiamiao Lu et al.   HUMAN GENE THERAPY

Lentiviral vectors can be used for full-length dystrophin gene therapy

(2017) John R. Counsell et al.   Scientific Reports

Gene Therapy for “Bubble Boy” Disease

(2016) Jonathan Hoggatt   CELL

Long-term, high-level hepatic secretion of acid α-glucosidase for Pompe disease achieved in non-human primates using helper-dependent adenovirus

(2016) D P W Rastall et al.   GENE THERAPY

Construction of minicircle DNA vectors capable of correcting familial hypercholesterolemia phenotype in a LDLR-deficient mouse model

(2016) X Hou et al.   GENE THERAPY

Late-Breaking Abstract

(2016)   HAEMOPHILIA

Adherence to prophylactic treatment in patients with haemophilia in Germany

(2016) W. Miesbach et al.   HAEMOPHILIA

Gene Therapy for Hemophilia

(2016) Arthur W. Nienhuis et al.   HUMAN GENE THERAPY

Augmenter of Liver Regeneration Gene Therapy Using a Novel Minicircle DNA Vector Alleviates Liver Fibrosis in Rats

(2016) Xin Wu et al.   HUMAN GENE THERAPY

Adeno-Associated Virus Gene Therapy for Liver Disease

(2016) Lisa M. Kattenhorn et al.   HUMAN GENE THERAPY

Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria

(2016) Delia D’Avola et al.   JOURNAL OF HEPATOLOGY

Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11

(2016) Lauriel F. Earley et al.   JOURNAL OF VIROLOGY

Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid

(2016) Koen Vercauteren et al.   MOLECULAR THERAPY

AAVR: A Multi-Serotype Receptor for AAV

(2016) Candace Summerford et al.   MOLECULAR THERAPY

Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293 Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and FLT1 Clinical Vector

(2016) Joshua C Grieger et al.   MOLECULAR THERAPY

In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy

(2016) Sourav R Choudhury et al.   MOLECULAR THERAPY

An essential receptor for adeno-associated virus infection

(2016) S. Pillay et al.   NATURE

Early clinical data raise the bar for hemophilia gene therapies

(2016) Elie Dolgin   NATURE BIOTECHNOLOGY

Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain

(2016) Benjamin E Deverman et al.   NATURE BIOTECHNOLOGY

A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice

(2016) Yang Yang et al.   NATURE BIOTECHNOLOGY

Studying Closed Hydrodynamic Models of “In Vivo” DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans

(2016) Luis Sendra et al.   PLoS One

Paying for future success in gene therapy

(2016) S. H. Orkin et al.   SCIENCE

Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1

(2016) Raymond D. Hickey et al.   Science Translational Medicine

Treating Immunodeficiency through HSC Gene Therapy

(2016) Claire Booth et al.   TRENDS IN MOLECULAR MEDICINE

Fetal Gene Therapy for Ornithine Transcarbamylase Deficiency by Intrahepatic Plasmid DNA-Micro-Bubble Injection Combined with Hepatic Ultrasound Insonation

(2016) Yoshie Oishi et al.   ULTRASOUND IN MEDICINE AND BIOLOGY

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

(2016) Takeshi Yokoo et al.   WORLD JOURNAL OF GASTROENTEROLOGY

Recent advances in oncolytic adenovirus therapies for cancer

(2016) Amanda Rosewell Shaw et al.   Current Opinion in Virology

Interaction of vectors and parental viruses with the host genome

(2016) Irene Gil-Farina et al.   Current Opinion in Virology

Cellular transduction mechanisms of adeno-associated viral vectors

(2016) Garrett Edward Berry et al.   Current Opinion in Virology

Investor Outlook: Solving Gene Therapy Pricing…with a Cures Voucher?

(2016) Joshua Schimmer et al.   Human Gene Therapy Clinical Development

Dynamics of antigen presentation to transgene product-specific CD4+ T cells and of Treg induction upon hepatic AAV gene transfer

(2016) George Q Perrin et al.   Molecular Therapy-Methods & Clinical Development

Manufacturing of recombinant adeno-associated viral vectors for clinical trials

(2016) Nathalie Clément et al.   Molecular Therapy-Methods & Clinical Development

Viral Vectors for Gene Therapy: Translational and Clinical Outlook

(2015) Melissa A. Kotterman et al.   Annual Review of Biomedical Engineering

Clinical Hepatocyte Transplantation: Practical Limits and Possible Solutions

(2015) Roberto Gramignoli et al.   EUROPEAN SURGICAL RESEARCH

Strategies to circumvent humoral immunity to adeno-associated viral vectors

(2015) Longping V Tse et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1

(2015) R Castello et al.   GENE THERAPY

Socio-economic burden of rare diseases: A systematic review of cost of illness evidence

(2015) Aris Angelis et al.   HEALTH POLICY

Modeling correction of severe urea cycle defects in the growing murine liver using a hybrid recombinant adeno-associated virus/piggyBactransposase gene delivery system

(2015) Sharon C. Cunningham et al.   HEPATOLOGY

Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers

(2015) Ziying Yan et al.   HUMAN GENE THERAPY

Adeno-Associated Virus Type 2 and Hepatocellular Carcinoma?

(2015) Kenneth I. Berns et al.   HUMAN GENE THERAPY

Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy

(2015) Randy J. Chandler et al.   JOURNAL OF CLINICAL INVESTIGATION

Adeno-Associated Virus Vector–Based Gene Therapy for Monogenetic Metabolic Diseases of the Liver

(2015) Norman Junge et al.   JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION

Cost-effectiveness of liver transplantation in methylmalonic and propionic acidemias

(2015) Meng Li et al.   LIVER TRANSPLANTATION

Comparative Study of Liver Gene Transfer With AAV Vectors Based on Natural and Engineered AAV Capsids

(2015) Lili Wang et al.   MOLECULAR THERAPY

Adeno-associated Vector Toxicity—To Be or Not to Be?

(2015) Hildegard Büning et al.   MOLECULAR THERAPY

The payers' perspective on gene therapies

(2015) Nicolas Touchot et al.   NATURE BIOTECHNOLOGY

Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

(2015) Jean-Charles Nault et al.   NATURE GENETICS

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

(2015) Alessio Cantore et al.   Science Translational Medicine

How ready are european payers for ema adaptive pathways?

(2015) R Macaulay   VALUE IN HEALTH

Progresses towards safe and efficient gene therapy vectors

(2015) Sergiu Chira et al.   Oncotarget

Recombinant adeno-associated virus vectors in the treatment of rare diseases

(2015) Eric Hastie et al.   Expert Opinion on Orphan Drugs

The Challenge for Gene Therapy: Innate Immune Response to Adenoviruses

(2015) Bart Thaci et al.   Oncotarget

A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII

(2014) S. A. Fahs et al.   BLOOD

Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

(2014) William Wold et al.   CURRENT GENE THERAPY

AAVrh.10 immunogenicity in mice and humans. Relevance of antibody cross-reactivity in human gene therapy

(2014) R Thwaite et al.   GENE THERAPY

Treatment of phenylketonuria using minicircle-based naked-DNA gene transfer to murine liver

(2014) Hiu Man Viecelli et al.   HEPATOLOGY

Adenovirus-Based Vaccines for Fighting Infectious Diseases and Cancer: Progress in the Field

(2014) Dragomira Majhen et al.   HUMAN GENE THERAPY

Medical research: Gene-therapy reboot

(2014) Laura Cassiday   NATURE

Engineering adeno-associated viruses for clinical gene therapy

(2014) Melissa A. Kotterman et al.   NATURE REVIEWS GENETICS

Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

(2014) Amit C. Nathwani et al.   NEW ENGLAND JOURNAL OF MEDICINE

Extensive double humanization of both liver and hematopoiesis in FRGN mice

(2014) Elizabeth M. Wilson et al.   Stem Cell Research

Liver zonation: Novel aspects of its regulation and its impact on homeostasis

(2014) Rolf Gebhardt   WORLD JOURNAL OF GASTROENTEROLOGY

Correction of Hyperbilirubinemia in Gunn Rats by Surgical Delivery of Low Doses of Helper-Dependent Adenoviral Vectors

(2014) Françoise Schmitt et al.   Human Gene Therapy Methods

Costs and utilization of hemophilia A and B patients with and without inhibitors

(2014) Edward P. Armstrong et al.   JOURNAL OF MEDICAL ECONOMICS

AAV-Mediated Gene Therapy for Research and Therapeutic Purposes

(2014) R. Jude Samulski et al.   Annual Review of Virology

Clinical Development of Gene Therapy Needs a Tailored Approach: A Regulatory Perspective from the European Union

(2014) Gopalan Narayanan et al.   Human Gene Therapy Clinical Development

B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study

(2014) M Corti et al.   Molecular Therapy-Methods & Clinical Development

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

(2013) F. Mingozzi et al.   BLOOD

Gene therapy for PIDs: Progress, pitfalls and prospects

(2013) Sayandip Mukherjee et al.   GENE

History of gene therapy

(2013) Thomas Wirth et al.   GENE

Role of antigen-specific regulatory CD4+CD25+ T cells in tolerance induction after neonatal IP administration of AAV-hF.IX

(2013) Y Shi et al.   GENE THERAPY

Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies

(2013) F D Ledley et al.   GENE THERAPY

Anti-Dystrophin T Cell Responses in Duchenne Muscular Dystrophy: Prevalence and a Glucocorticoid Treatment Effect

(2013) Kevin M. Flanigan et al.   HUMAN GENE THERAPY

Triple Trans-Splicing Adeno-Associated Virus Vectors Capable of Transferring the Coding Sequence for Full-Length Dystrophin Protein into Dystrophic Mice

(2013) Taeyoung Koo et al.   HUMAN GENE THERAPY

Helper-dependent adenoviral liver gene therapy protects against induced attacks and corrects protein folding stress in acute intermittent porphyria mice

(2013) Carmen Unzu et al.   HUMAN MOLECULAR GENETICS

Patient monitoring and follow-up in lentiviral clinical trials

(2013) Gerard J. McGarrity et al.   JOURNAL OF GENE MEDICINE

Gene therapy clinical trials worldwide to 2012 - an update

(2013) Samantha L. Ginn et al.   JOURNAL OF GENE MEDICINE

Differential Type I Interferon-dependent Transgene Silencing of Helper-dependent Adenoviral vs. Adeno-associated Viral Vectors In Vivo

(2013) Masataka Suzuki et al.   MOLECULAR THERAPY

The Fetal Mouse Is a Sensitive Genotoxicity Model That Exposes Lentiviral-associated Mutagenesis Resulting in Liver Oncogenesis

(2013) Ali Nowrouzi et al.   MOLECULAR THERAPY

Platelet Gene Therapy by Lentiviral Gene Delivery to Hematopoietic Stem Cells Restores Hemostasis and Induces Humoral Immune Tolerance in FIXnull Mice

(2013) Yingyu Chen et al.   MOLECULAR THERAPY

Integration-deficient Lentiviral Vectors Expressing Codon-optimized R338L Human FIX Restore Normal Hemostasis in Hemophilia B Mice

(2013) Thipparat Suwanmanee et al.   MOLECULAR THERAPY

Transduction of Fetal Mice With a Feline Lentiviral Vector Induces Liver Tumors Which Exhibit an E2F Activation Signature

(2013) Reba Condiotti et al.   MOLECULAR THERAPY

Plasmapheresis Eliminates the Negative Impact of AAV Antibodies on Microdystrophin Gene Expression Following Vascular Delivery

(2013) LG Chicoine et al.   MOLECULAR THERAPY

Selection and evaluation of clinically relevant AAV variants in a xenograft liver model

(2013) Leszek Lisowski et al.   NATURE

A largely random AAV integration profile after LPLD gene therapy

(2013) Christine Kaeppel et al.   NATURE MEDICINE

Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy

(2013) A. Biffi et al.   SCIENCE

Immune responses in liver-directed lentiviral gene therapy

(2013) Andrea Annoni et al.   Translational Research

Pre-existing Anti–Adeno-Associated Virus Antibodies as a Challenge in AAV Gene Therapy

(2013) Vedell Louis Jeune et al.   Human Gene Therapy Methods

Humoral Immune Response to AAV

(2013) Roberto Calcedo et al.   Frontiers in Immunology

Lessons Learned from the Clinical Development and Market Authorization of Glybera

(2013) Laura M. Bryant et al.   Human Gene Therapy Clinical Development

Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer

(2012) G. Buchlis et al.   BLOOD

Reversal of Metabolic and Neurological Symptoms of Phenylketonuric Mice Treated with a PAH Containing Helper-Dependent Adenoviral Vector

(2012) Monica Cerreto et al.   CURRENT GENE THERAPY

Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue

(2012) F Mingozzi et al.   GENE THERAPY

Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity

(2012) E. L. KUETHER et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Properties of the Adeno-Associated Virus Assembly-Activating Protein

(2012) M. Naumer et al.   JOURNAL OF VIROLOGY

Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

(2012) Federico Mingozzi et al.   MOLECULAR THERAPY

Suggested guidelines for the diagnosis and management of urea cycle disorders

(2012) Johannes Häberle et al.   Orphanet Journal of Rare Diseases

Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions

(2012) Mahmoud Elsabahy et al.   Current Drug Delivery

Adeno-Associated Virus Antibody Profiles in Newborns, Children, and Adolescents

(2011) Roberto Calcedo et al.   Clinical and Vaccine Immunology

Immune Responses to AAV in Clinical Trials

(2011) Federico Mingozzi et al.   CURRENT GENE THERAPY

Perinatal Gene Transfer to the Liver

(2011) Tristan R. McKay et al.   CURRENT PHARMACEUTICAL DESIGN

Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine

(2011) J H McIntosh et al.   GENE THERAPY

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia

(2011) B Crane et al.   GENE THERAPY

Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia

(2011) C Li et al.   GENE THERAPY

Phase 2 Clinical Trial of a Recombinant Adeno-Associated Viral Vector Expressing α1-Antitrypsin: Interim Results

(2011) Terence R. Flotte et al.   HUMAN GENE THERAPY

Helper-dependent adenoviral vectors for liver-directed gene therapy

(2011) N. Brunetti-Pierri et al.   HUMAN MOLECULAR GENETICS

Inverse zonation of hepatocyte transduction with AAV vectors between mice and non-human primates

(2011) Peter Bell et al.   MOLECULAR GENETICS AND METABOLISM

Induction and Prevention of Severe Hyperammonemia in the spfash Mouse Model of Ornithine Transcarbamylase Deficiency Using shRNA and rAAV-mediated Gene Delivery

(2011) Sharon C Cunningham et al.   MOLECULAR THERAPY

A 10 Patient Case Report on the Impact of Plasmapheresis Upon Neutralizing Factors Against Adeno-associated Virus (AAV) Types 1, 2, 6, and 8

(2011) Virginie Monteilhet et al.   MOLECULAR THERAPY

Stable Human FIX Expression After 0.9G Intrauterine Gene Transfer of Self-complementary Adeno-associated Viral Vector 5 and 8 in Macaques

(2011) Citra NZ Mattar et al.   MOLECULAR THERAPY

Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid Proteins

(2011) Amit C Nathwani et al.   MOLECULAR THERAPY

State-of-the-art gene-based therapies: the road ahead

(2011) Mark A. Kay   NATURE REVIEWS GENETICS

Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII

(2011) Chuhong Hu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Activation of the NF-κB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy

(2011) Giridhara R. Jayandharan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Development of a recombinant adenovirus vector production system free of replication-competent adenovirus by utilizing a packaging size limit of the viral genome

(2011) Takayuki Suzuki et al.   VIRUS RESEARCH

Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors

(2010) Sylvie Boutin et al.   HUMAN GENE THERAPY

AAV plasmid DNA simplifies liver-directed in vivo gene therapy: comparison of expression levels after plasmid DNA-, adeno-associated virus- and adenovirus-mediated liver transfection

(2010) Axel Doenecke et al.   JOURNAL OF GENE MEDICINE

Chromosomal Integration of Adenoviral Vector DNA In Vivo

(2010) S. L. Stephen et al.   JOURNAL OF VIROLOGY

Proteasome Inhibitors Enhance Gene Delivery by AAV Virus Vectors Expressing Large Genomes in Hemophilia Mouse and Dog Models: A Strategy for Broad Clinical Application

(2010) Paul E Monahan et al.   MOLECULAR THERAPY

A robust system for production of minicircle DNA vectors

(2010) Mark A Kay et al.   NATURE BIOTECHNOLOGY

20 years of gene therapy for SCID

(2010) Alain Fischer et al.   NATURE IMMUNOLOGY

Ex Vivo Liver – Directed Gene Therapy for the Treatment of Metabolic Diseases: Advances in Hepatocyte Transplantation and Retroviral Vectors

(2009) Tuan Nguyen et al.   CURRENT GENE THERAPY

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

(2009) A A Rahim et al.   GENE THERAPY

Hepatic regulatory T cells and Kupffer cells are crucial mediators of systemic T cell tolerance to antigens targeting murine liver

(2009) Ekaterina Breous et al.   HEPATOLOGY

Improved Induction of Immune Tolerance to Factor IX by Hepatic AAV-8 Gene Transfer

(2009) Mario Cooper et al.   HUMAN GENE THERAPY

Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors

(2009) Gary C. Pien et al.   JOURNAL OF CLINICAL INVESTIGATION

Worldwide Epidemiology of Neutralizing Antibodies to Adeno‐Associated Viruses

(2009) Roberto Calcedo et al.   JOURNAL OF INFECTIOUS DISEASES

Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency

(2009) James M. Wilson   MOLECULAR GENETICS AND METABOLISM

Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy

(2009) M. L. Brantly et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

(2009) N. Cartier et al.   SCIENCE

Pediatric liver transplantation

(2009) Marco Spada et al.   WORLD JOURNAL OF GASTROENTEROLOGY

Adenovirus Serotype 5 Hexon Mediates Liver Gene Transfer

(2008) Simon N. Waddington et al.   CELL

Immunity to adeno-associated virus vectors in animals and humans: a continued challenge

(2008) A K Zaiss et al.   GENE THERAPY

Erythroid-specific Human Factor IX Delivery From In Vivo Selected Hematopoietic Stem Cells Following Nonmyeloablative Conditioning in Hemophilia B Mice

(2008) Alex H Chang et al.   MOLECULAR THERAPY

Gene Delivery to the Juvenile Mouse Liver Using AAV2/8 Vectors

(2008) Sharon C Cunningham et al.   MOLECULAR THERAPY

Substitution of Hexon Hypervariable Region 5 of Adenovirus Serotype 5 Abrogates Blood Factor Binding and Limits Gene Transfer to Liver

(2008) Frédéric Vigant et al.   MOLECULAR THERAPY

Self-complementary AAV Vectors; Advances and Applications

(2008) Douglas M McCarty   MOLECULAR THERAPY

Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis

(2008) Albert M. Maguire et al.   NEW ENGLAND JOURNAL OF MEDICINE

Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

(2008) James W.B. Bainbridge et al.   NEW ENGLAND JOURNAL OF MEDICINE

Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo

(2008) O. Kalyuzhniy et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics

(2008) A. V. Cideciyan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA