Overcoming innate immune barriers that impede AAV gene therapy vectors

Codon Modification and PAMPs in Clinical AAV Vectors: The Tortoise or the Hare?

(2020) J. Fraser Wright   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

Management of Neuroinflammatory Responses to AAV-Mediated Gene Therapies for Neurodegenerative Diseases

(2020) Barbara A. Perez et al.   Brain Sciences

Revisiting the “New” Inflammatory Toxicities of Adeno-Associated Virus Vectors

(2020) Terence R. Flotte   HUMAN GENE THERAPY

mtDNA Activates cGAS Signaling and Suppresses the YAP-Mediated Endothelial Cell Proliferation Program to Promote Inflammatory Injury

(2020) Long Shuang Huang et al.   IMMUNITY

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

(2020) Christian Leborgne et al.   NATURE MEDICINE

Methods Matter -- Standard Production Platforms for Recombinant AAV Produce Chemically and Functionally Distinct Vectors

(2020) Neil G. Rumachik et al.   Molecular Therapy-Methods & Clinical Development

Moving Forward After Two Deaths in a Gene Therapy Trial of Myotubular Myopathy

(2020) James M. Wilson et al.   HUMAN GENE THERAPY

AAV Vectors: Are They Safe?

(2020) Arun Srivastava   HUMAN GENE THERAPY

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

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

Adeno-associated Virus (AAV) versus Immune Response

(2019) Joseph Rabinowitz et al.   Viruses-Basel

Adeno-associated virus vector as a platform for gene therapy delivery

(2019) Dan Wang et al.   NATURE REVIEWS DRUG DISCOVERY

Structural basis of STING binding with and phosphorylation by TBK1

(2019) Conggang Zhang et al.   NATURE

Induction of Selenoprotein P mRNA during Hepatitis C Virus Infection Inhibits RIG-I-Mediated Antiviral Immunity

(2019) Kazuhisa Murai et al.   Cell Host & Microbe

TLR9-activating CpG-B ODN but not TLR7 Agonists Trigger Antibody Formation to Factor IX in Muscle Gene Transfer

(2019) John S.S. Butterfield et al.   Human Gene Therapy Methods

Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes

(2019) Jung Hwan Bae et al.   Cells

Onasemnogene Abeparvovec: First Global Approval

(2019) Sheridan M. Hoy   DRUGS

Charge-Mediated Pyrin Oligomerization Nucleates Antiviral IFI16 Sensing of Herpesvirus DNA

(2019) Krystal K. Lum et al.   mBio

A Human Long Non-coding RNA LncATV Promotes Virus Replication Through Restricting RIG-I–Mediated Innate Immunity

(2019) Jingjing Fan et al.   Frontiers in Immunology

Enhancement of Adeno-Associated Virus-Mediated Gene Therapy Using Hydroxychloroquine in Murine and Human Tissues

(2019) Laurel C. Chandler et al.   Molecular Therapy-Methods & Clinical Development

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

(2019) Pierce J. Ogden et al.   SCIENCE

Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage

(2019) Claire Moreuil et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

TLR9 signaling mediates adaptive immunity following systemic AAV gene therapy

(2019) Scott N. Ashley et al.   CELLULAR IMMUNOLOGY

Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN

(2018) Christian Hinderer et al.   HUMAN GENE THERAPY

Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity

(2018) Nicole K. Paulk et al.   MOLECULAR THERAPY

Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions In Vivo

(2018) Xiaolei Pei et al.   Frontiers in Immunology

A Rationally Engineered Capsid Variant of AAV9 for Systemic CNS-Directed and Peripheral Tissue-Detargeted Gene Delivery in Neonates

(2018) Dan Wang et al.   Molecular Therapy-Methods & Clinical Development

Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Iduronate-2-Sulfatase in Rhesus Macaques

(2018) Juliette Hordeaux et al.   Molecular Therapy-Methods & Clinical Development

Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Human Alpha-L-Iduronidase in Rhesus Macaques

(2018) Juliette Hordeaux et al.   Molecular Therapy-Methods & Clinical Development

Synergistic and independent action of endogenous microRNAs 122a and 199a for post-transcriptional liver detargeting of gene vectors

(2018) Bijay Dhungel et al.   Scientific Reports

Innate Sensing of DNA Virus Genomes

(2018) Zhe Ma et al.   Annual Review of Virology

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

(2018) Amine Meliani et al.   Nature Communications

Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial

(2017) Céline Vandamme et al.   HUMAN GENE THERAPY

Inhibition of antigen presentation during AAV gene therapy using virus peptides

(2017) Wenwei Shao et al.   HUMAN MOLECULAR GENETICS

RNA sensors of the innate immune system and their detection of pathogens

(2017) Nanhua Chen et al.   IUBMB LIFE

AAV8 Can Induce Innate and Adaptive Immune Response in the Primate Eye

(2017) Felix F. Reichel et al.   MOLECULAR THERAPY

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein–DNA ladders

(2017) Liudmila Andreeva et al.   NATURE

The complement system as a potential therapeutic target in rheumatic disease

(2017) Leendert A. Trouw et al.   Nature Reviews Rheumatology

Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy

(2017) Jerry R. Mendell 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

IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP

(2017) K. L. Jønsson et al.   Nature Communications

IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes

(2017) Jessica F. Almine et al.   Nature Communications

Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles

(2016) Takashi K. Kishimoto et al.   Nature Nanotechnology

The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury

(2016) Bo Hu et al.   SCIENCE

DNA sensor cGAS-mediated immune recognition

(2016) Pengyan Xia et al.   Protein & Cell

Innate Immune Pattern Recognition: A Cell Biological Perspective

(2015) Sky W. Brubaker et al.   Annual Review of Immunology

The nucleic acid-sensing inflammasomes

(2015) Tsan Sam Xiao   IMMUNOLOGICAL REVIEWS

Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase–DNA Interaction

(2015) Jie An et al.   JOURNAL OF IMMUNOLOGY

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

cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection

(2015) Megan H. Orzalli et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RIG-I in RNA virus recognition

(2015) Alison M. Kell et al.   VIROLOGY

The Status ofRPE65Gene Therapy Trials: Safety and Efficacy

(2015) Eric A. Pierce et al.   Cold Spring Harbor Perspectives in Medicine

The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex

(2015) Sarah A Stratmann et al.   eLife

Complement System Part I – Molecular Mechanisms of Activation and Regulation

(2015) Nicolas S. Merle et al.   Frontiers in Immunology

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

Basic Biology of Adeno-Associated Virus (AAV) Vectors Used in Gene Therapy

(2014) Balaji Balakrishnan et al.   CURRENT GENE THERAPY

Cytosolic RNA:DNA hybrids activate the cGAS–STING axis

(2014) Arun K Mankan et al.   EMBO JOURNAL

Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates

(2014) M A Kotterman et al.   GENE THERAPY

Adenovirus Vector-Induced Innate Inflammatory Mediators, MAPK Signaling, As Well As Adaptive Immune Responses Are Dependent upon Both TLR2 and TLR9 In Vivo

(2014) D. M. Appledorn et al.   JOURNAL OF IMMUNOLOGY

Complement modulation of T cell immune responses during homeostasis and disease

(2014) Elizabeth V. Clarke et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Innate Nuclear Sensor IFI16 Translocates into the Cytoplasm during the Early Stage of In Vitro Human Cytomegalovirus Infection and Is Entrapped in the Egressing Virions during the Late Stage

(2014) V. Dell'Oste et al.   JOURNAL OF VIROLOGY

The SKIV2L RNA exosome limits activation of the RIG-I-like receptors

(2014) Sterling C Eckard et al.   NATURE IMMUNOLOGY

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

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

Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance

(2014) Roberto A. Maldonado et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Toll-Like Receptor Signaling Pathways

(2014) Takumi Kawasaki et al.   Frontiers in Immunology

Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells

(2013) A. T. Martino et al.   BLOOD

Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase

(2013) Pu Gao et al.   CELL

Global CNS gene delivery and evasion of anti-AAV-neutralizing antibodies by intrathecal AAV administration in non-human primates

(2013) S J Gray et al.   GENE THERAPY

Prolonged Gene Expression in Muscle Is Achieved Without Active Immune Tolerance Using MicrorRNA 142.3p-Regulated rAAV Gene Transfer

(2013) Florence Boisgerault et al.   HUMAN GENE THERAPY

Kinetics of Adeno-Associated Virus Serotype 2 (AAV2) and AAV8 Capsid Antigen Presentation In Vivo Are Identical

(2013) Yi He et al.   HUMAN GENE THERAPY

Cytosolic Sensing of Viruses

(2013) Delphine Goubau et al.   IMMUNITY

Master sensors of pathogenic RNA – RIG-I like receptors

(2013) Martin Schlee   IMMUNOBIOLOGY

Adeno-associated virus capsid antigen presentation is dependent on endosomal escape

(2013) Chengwen Li et al.   JOURNAL OF CLINICAL INVESTIGATION

CpG-depleted adeno-associated virus vectors evade immune detection

(2013) Susan M. Faust et al.   JOURNAL OF CLINICAL INVESTIGATION

Mir-142-3p target sequences reduce transgene-directed immunogenicity following intramuscular adeno-associated virus 1 vector-mediated gene delivery

(2013) Anna Majowicz et al.   JOURNAL OF GENE MEDICINE

Synthetic Oligodeoxynucleotides Containing Suppressive TTAGGG Motifs Inhibit AIM2 Inflammasome Activation

(2013) J. J. Kaminski et al.   JOURNAL OF IMMUNOLOGY

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

(2013) LG Chicoine et al.   MOLECULAR THERAPY

Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome

(2013) C.M. Legendre et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA

(2013) M. H. Orzalli et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects

(2013) X.-D. Li et al.   SCIENCE

In Vivo-Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous

(2013) D. Dalkara et al.   Science Translational Medicine

Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys

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

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

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

Bioengineering of AAV2 Capsid at Specific Serine, Threonine, or Lysine Residues Improves Its Transduction Efficiency in Vitro and in Vivo

(2013) Nishanth Gabriel et al.   Human Gene Therapy Methods

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

(2012) F Mingozzi et al.   GENE THERAPY

Regulation of Humoral Immunity by Complement

(2012) Michael C. Carroll et al.   IMMUNITY

Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor

(2012) Tengchuan Jin et al.   IMMUNITY

Single Amino Acid Modification of Adeno-Associated Virus Capsid Changes Transduction and Humoral Immune Profiles

(2012) C. Li et al.   JOURNAL OF VIROLOGY

MyD88 Signaling in B Cells Regulates the Production of Th1-dependent Antibodies to AAV

(2012) Muriel Sudres et al.   MOLECULAR THERAPY

Minimizing the Inhibitory Effect of Neutralizing Antibody for Efficient Gene Expression in the Liver With Adeno-associated Virus 8 Vectors

(2012) Jun Mimuro et al.   MOLECULAR THERAPY

Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

(2012) L. Sun et al.   SCIENCE

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

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

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

Adeno-Associated Virus Serotype 9 Transduction in the Central Nervous System of Nonhuman Primates

(2011) Lluis Samaranch et al.   HUMAN GENE THERAPY

Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity

(2011) Taro Kawai et al.   IMMUNITY

Mechanism of Endosomal TLR Inhibition by Antimalarial Drugs and Imidazoquinolines

(2011) A. Kuznik et al.   JOURNAL OF IMMUNOLOGY

Dangers Within: DAMP Responses to Damage and Cell Death in Kidney Disease

(2011) D. L. Rosin et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

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

Self-complementary AAVs Induce More Potent Transgene Product-specific Immune Responses Compared to a Single-stranded Genome

(2011) TeLang Wu et al.   MOLECULAR THERAPY

Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges

(2011) Federico Mingozzi et al.   NATURE REVIEWS GENETICS

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

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

Innate Immune Responses to AAV Vectors

(2011) Geoffrey L. Rogers et al.   Frontiers in Microbiology

Pattern Recognition Receptors and Inflammation

(2010) Osamu Takeuchi et al.   CELL

The complement system

(2010) J. Vidya Sarma et al.   CELL AND TISSUE RESEARCH

Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver

(2010) C Qiao et al.   GENE THERAPY

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

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

AAV Vectors Avoid Inflammatory Signals Necessary to Render Transduced Hepatocyte Targets for Destructive T Cells

(2010) Suryanarayan Somanathan et al.   MOLECULAR THERAPY

MicroRNA-regulated, Systemically Delivered rAAV9: A Step Closer to CNS-restricted Transgene Expression

(2010) Jun Xie et al.   MOLECULAR THERAPY

The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors

(2010) Taro Kawai et al.   NATURE IMMUNOLOGY

Innate Immune Recognition of Viruses and Viral Vectors

(2009) Xiaopei Huang et al.   HUMAN GENE THERAPY

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

Proteasome Inhibitors Decrease AAV2 Capsid derived Peptide Epitope Presentation on MHC Class I Following Transduction

(2009) Jonathan D Finn et al.   MOLECULAR THERAPY

AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC

(2009) Veit Hornung et al.   NATURE

STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

(2009) Hiroki Ishikawa et al.   NATURE

Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands

(2009) Roman Barbalat et al.   NATURE IMMUNOLOGY

Variation matters: TLR structure and species-specific pathogen recognition

(2009) Dirk Werling et al.   TRENDS IN IMMUNOLOGY

A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infection

(2008) M. Quigley et al.   BLOOD

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

(2008) A K Zaiss et al.   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

In Vitro and In Vivo Gene Therapy Vector Evolution via Multispecies Interbreeding and Retargeting of Adeno-Associated Viruses

(2008) D. Grimm et al.   JOURNAL OF VIROLOGY

Self-complementary AAV Vectors; Advances and Applications

(2008) Douglas M McCarty   MOLECULAR THERAPY

Next generation of adeno-associated virus 2 vectors: Point mutations in tyrosines lead to high-efficiency transduction at lower doses

(2008) L. Zhong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

(2008) Li Zhong et al.   VIROLOGY