Emerging Immunogenicity and Genotoxicity Considerations of Adeno-Associated Virus Vector Gene Therapy for Hemophilia

Overcoming innate immune barriers that impede AAV gene therapy vectors

(2021) Manish Muhuri et al.   JOURNAL OF CLINICAL INVESTIGATION

Immune Responses to Viral Gene Therapy Vectors

(2020) Jamie L. Shirley et al.   MOLECULAR THERAPY

AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer

(2020) Helena Costa Verdera et al.   MOLECULAR THERAPY

Engineering adeno-associated virus vectors for gene therapy

(2020) Chengwen Li et al.   NATURE REVIEWS GENETICS

Capsid-specific removal of circulating antibodies to adeno-associated virus vectors

(2020) Berangere Bertin et al.   Scientific Reports

Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation

(2020) Céline Vandamme et al.   Frontiers in Immunology

Successful Transduction with AAV Vectors after Selective Depletion of Anti-AAV Antibodies by Immunoadsorption

(2020) Alejandro Orlowski et al.   Molecular Therapy-Methods & Clinical Development

IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies

(2020) Christian Leborgne et al.   NATURE MEDICINE

Translational Potential of Immune Tolerance Induction by AAV Liver-Directed Factor VIII Gene Therapy for Hemophilia A

(2020) Benjamin J. Samelson-Jones et al.   Frontiers in Immunology

The critical need for postmarketing surveillance in gene therapy for haemophilia

(2020) Barbara A. Konkle et al.   HAEMOPHILIA

WFH Guidelines for the Management of Hemophilia, 3rd edition

(2020) Alok Srivastava et al.   HAEMOPHILIA

Long-Term Follow-Up of the First in Human Intravascular Delivery of AAV for Gene Transfer: AAV2-hFIX16 for Severe Hemophilia B

(2020) Lindsey A. George et al.   MOLECULAR THERAPY

Quantification of CpG Motifs in rAAV Genomes: Avoiding the Toll

(2020) J. Fraser Wright   MOLECULAR THERAPY

Timing of Intensive Immunosuppression Impacts Risk of Transgene Antibodies after AAV Gene Therapy in Nonhuman Primates

(2020) Benjamin J. Samelson-Jones et al.   Molecular Therapy-Methods & Clinical Development

BAX 335 hemophilia B gene therapy clinical trial results - potential impact of CpG sequences on gene expression

(2020) Barbara A Konkle et al.   BLOOD

Liver injury increases incidence of HCC following AAV gene therapy in mice

(2020) Dhwanil A. Dalwadi et al.   MOLECULAR THERAPY

Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme

(2020) Zachary C. Elmore et al.   JCI Insight

First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies

(2020) Steven W. Pipe et al.   BLOOD

The Identity of Human Tissue-Emigrant CD8+ T Cells

(2020) Marcus Buggert et al.   CELL

Early Phase Clinical Immunogenicity of Valoctocogene Roxaparvovec, an AAV5-Mediated Gene Therapy for Hemophilia A

(2020) Brian R. Long et al.   MOLECULAR THERAPY

Safety questions for AAV gene therapy

(2020) Charles P. Venditti   NATURE BIOTECHNOLOGY

A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells

(2020) Giang N. Nguyen et al.   NATURE BIOTECHNOLOGY

Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia

(2019) Flora Peyvandi et al.   HAEMOPHILIA

Adeno-associated virus in the liver: natural history and consequences in tumour development

(2019) Tiziana La Bella et al.   GUT

Hemophilia A and B: molecular and clinical similarities and differences

(2019) Giancarlo Castaman et al.   HAEMATOLOGICA

Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors

(2019) Anita Kruzik et al.   Molecular Therapy-Methods & Clinical Development

Type I IFN Sensing by cDCs and CD4+ T Cell Help Are Both Requisite for Cross-Priming of AAV Capsid-Specific CD8+ T Cells

(2019) Jamie L. Shirley et al.   MOLECULAR THERAPY

The Effect of CpG Sequences on Capsid-Specific CD8+ T Cell Responses to AAV Vector Gene Transfer

(2019) ZhiQuan Xiang et al.   MOLECULAR THERAPY

Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design

(2019) Pierce J. Ogden et al.   SCIENCE

Effects of codon optimization on coagulation factor IX translation and structure: Implications for protein and gene therapies

(2019) Aikaterini Alexaki et al.   Scientific Reports

Gene therapy for hemophilia

(2019) Amit C. Nathwani   Hematology-American Society of Hematology Education Program

Role of Regulatory T Cell and Effector T Cell Exhaustion in Liver-Mediated Transgene Tolerance in Muscle

(2019) Jérôme Poupiot et al.   Molecular Therapy-Methods & Clinical Development

Prevalence and long-term monitoring of humoral immunity against adeno-associated virus in Duchenne Muscular Dystrophy patients

(2018) Christian Leborgne et al.   CELLULAR IMMUNOLOGY

Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis

(2018) Geoffrey D. Keeler et al.   MOLECULAR THERAPY

Systemic AAV micro-dystrophin gene therapy for Duchenne muscular dystrophy

(2018) Dongsheng Duan   MOLECULAR THERAPY

Influence of Pre-existing Anti-capsid Neutralizing and Binding Antibodies on AAV Vector Transduction

(2018) Zachary Fitzpatrick et al.   Molecular Therapy-Methods & Clinical Development

Emerging Issues in AAV-Mediated In Vivo Gene Therapy

(2018) Pasqualina Colella et al.   Molecular Therapy-Methods & Clinical Development

Exposure to wild-type AAV drives distinct capsid immunity profiles in humans

(2018) Klaudia Kuranda et al.   JOURNAL OF CLINICAL INVESTIGATION

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

(2018) Amine Meliani et al.   Nature Communications

Strategy to detect pre-existing immunity to AAV gene therapy

(2017) L Falese et al.   GENE THERAPY

Gene Therapy for Hemophilia

(2017) Amit C. Nathwani et al.   HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA

Advances in Gene Therapy for Hemophilia

(2017) Amit C. Nathwani et al.   HUMAN GENE THERAPY

Alloantigen gene transfer to hepatocytes promotes tolerance to pancreatic islet graft by inducing CD8 + regulatory T cells

(2017) Valentin Le Guen et al.   JOURNAL OF HEPATOLOGY

IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation

(2017) Stanley C. Jordan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant

(2017) Lindsey A. George et al.   NEW ENGLAND JOURNAL OF MEDICINE

AAV5–Factor VIII Gene Transfer in Severe Hemophilia A

(2017) Savita Rangarajan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion

(2017) Longping Victor Tse et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

(2017) Alexandra Sherman et al.   Frontiers in Immunology

Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer

(2017) Roland W. Herzog et al.   CELLULAR IMMUNOLOGY

Men with severe hemophilia in the United States: birth cohort analysis of a large national database

(2016) M. A. Mazepa et al.   BLOOD

Presentation of hepatocellular antigens

(2016) Arash Grakoui et al.   Cellular & Molecular Immunology

Adeno-Associated Virus: The Naturally Occurring Virus Versus the Recombinant Vector

(2016) Arun Srivastava   HUMAN GENE THERAPY

Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B

(2016) Vijaya L Simhadri et al.   JOURNAL OF MEDICAL GENETICS

Wild-type AAV Insertions in Hepatocellular Carcinoma Do Not Inform Debate Over Genotoxicity Risk of Vectorized AAV

(2016) Jean-Charles Nault et al.   MOLECULAR THERAPY

Genotoxicity in Mice Following AAV Gene Delivery: A Safety Concern for Human Gene Therapy?

(2016) Randy J Chandler et al.   MOLECULAR THERAPY

AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

(2015) J. M. Crudele et al.   BLOOD

Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure

(2015) B Greenberg et al.   GENE THERAPY

Employing a Gain-of-Function Factor IX Variant R338L to Advance the Efficacy and Safety of Hemophilia B Human Gene Therapy: Preclinical Evaluation Supporting an Ongoing Adeno-Associated Virus Clinical Trial

(2015) Paul E. Monahan et al.   HUMAN GENE THERAPY

Decoding mechanisms by which silent codon changes influence protein biogenesis and function

(2015) Vedrana Bali et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

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

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

Unique Roles of TLR9- and MyD88-Dependent and -Independent Pathways in Adaptive Immune Responses to AAV-Mediated Gene Transfer

(2015) Geoffrey L. Rogers et al.   Journal of Innate Immunity

Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

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

Determination of Anti-Adeno-Associated Virus Vector Neutralizing Antibody Titer with anIn VitroReporter System

(2015) Amine Meliani et al.   Human Gene Therapy Methods

Evaluation of Readministration of a Recombinant Adeno-Associated Virus Vector Expressing Acid Alpha-Glucosidase in Pompe Disease: Preclinical to Clinical Planning

(2015) Manuela Corti et al.   Human Gene Therapy Clinical Development

AAV capsid CD8+ T-cell epitopes are highly conserved across AAV serotypes

(2015) Daniel J Hui et al.   Molecular Therapy-Methods & Clinical Development

Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors

(2014) Q Liu et al.   GENE THERAPY

Hepatitis B virus infection enhances susceptibility toward adeno-associated viral vector transductionin vitroandin vivo

(2014) Marianna Hösel et al.   HEPATOLOGY

Adeno-Associated Virus Serotype 1 (AAV1)- and AAV5-Antibody Complex Structures Reveal Evolutionary Commonalities in Parvovirus Antigenic Reactivity

(2014) Yu-Shan Tseng et al.   JOURNAL OF VIROLOGY

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

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

A critical analysis of codon optimization in human therapeutics

(2014) Vincent P. Mauro et al.   TRENDS IN MOLECULAR MEDICINE

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

Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant

(2013) J. McIntosh et al.   BLOOD

Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies

(2013) David M. Markusic et al.   EMBO Molecular Medicine

The prevalence of neutralizing antibodies against adeno-associated virus capsids is reduced in young Japanese individuals

(2013) Jun Mimuro et al.   JOURNAL OF MEDICAL VIROLOGY

C-Reactive Protein (CRP) Is Essential for Efficient Systemic Transduction of Recombinant Adeno-Associated Virus Vector 1 (rAAV-1) and rAAV-6 in Mice

(2013) J. Denard et al.   JOURNAL OF VIROLOGY

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

Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys

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

Building better drugs: developing and regulating engineered therapeutic proteins

(2013) Chava Kimchi-Sarfaty et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

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

(2012) F Mingozzi et al.   GENE THERAPY

Humoral and Cellular Capsid-Specific Immune Responses to Adeno-Associated Virus Type 1 in Randomized Healthy Donors

(2012) P. Veron et al.   JOURNAL OF IMMUNOLOGY

Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates

(2012) Carmen Unzu et al.   Journal of Translational Medicine

The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver

(2011) A. T. Martino et al.   BLOOD

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

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

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

(2011) C Li et al.   GENE THERAPY

Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors

(2011) Marianna Hösel et al.   HEPATOLOGY

Impact of Pre-Existing Immunity on Gene Transfer to Nonhuman Primate Liver with Adeno-Associated Virus 8 Vectors

(2011) Lili Wang et al.   HUMAN GENE 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

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

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

(2011) Amit C. Nathwani et al.   NEW ENGLAND JOURNAL OF MEDICINE

Assessing the potential for AAV vector genotoxicity in a murine model

(2010) H. Li et al.   BLOOD

Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy

(2010) J. D. Finn et al.   BLOOD

Codon optimization of human factor VIII cDNAs leads to high-level expression

(2010) N. J. Ward et al.   BLOOD

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

BALB/c Mice Show Impaired Hepatic Tolerogenic Response Following AAV Gene Transfer to the Liver

(2010) Ekaterina Breous et al.   MOLECULAR THERAPY

Preexisting Immunity and Low Expression in Primates Highlight Translational Challenges for Liver-directed AAV8-mediated Gene Therapy

(2010) Gregory D Hurlbut et al.   MOLECULAR THERAPY

Immune tolerance: What is unique about the liver

(2009) Gisa Tiegs et al.   JOURNAL OF AUTOIMMUNITY

The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice

(2009) Jiangao Zhu et al.   JOURNAL OF CLINICAL INVESTIGATION

Worldwide Epidemiology of Neutralizing Antibodies to Adeno‐Associated Viruses

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

X-Linked Thrombophilia with a Mutant Factor IX (Factor IX Padua)

(2009) Paolo Simioni et al.   NEW ENGLAND JOURNAL OF MEDICINE

How we treat a hemophilia A patient with a factor VIII inhibitor

(2008) C. L. Kempton et al.   BLOOD

Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy

(2008) G. P. Niemeyer et al.   BLOOD

Adeno-associated virus integration: virus versus vector

(2008) R H Smith   GENE THERAPY

Why does the mutationG17736AVal107Val (silent) in theF9gene cause mild haemophilia B in five Swedish families?

(2008) K. E. KNOBE et al.   HAEMOPHILIA

Adenovirus-Based Vaccines Generate Cytotoxic T Lymphocytes to Epitopes of NS1 from Dengue Virus That Are Present in All Major Serotypes

(2008) Guangping Gao et al.   HUMAN GENE THERAPY

Complement Is an Essential Component of the Immune Response to Adeno-Associated Virus Vectors

(2008) A. K. Zaiss et al.   JOURNAL OF VIROLOGY

Optimization of Self-complementary AAV Vectors for Liver-directed Expression Results in Sustained Correction of Hemophilia B at Low Vector Dose

(2007) Zhijian Wu et al.   MOLECULAR THERAPY