4.8 Article

Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing

Related references

Note: Only part of the references are listed.
Article Neurosciences

AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset

David Goertsen et al.

Summary: The study developed AAV capsids that achieved robust transgene expression in the brain with decreased liver targeting after non-invasive administration, enabling more targeted systemic gene delivery. This organ-specific targeting extends to marmosets, allowing for non-invasive gene delivery with distinct transgene expression patterns. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates opens up new avenues for basic research and therapeutic possibilities beyond naturally occurring serotypes.

NATURE NEUROSCIENCE (2022)

Review Biochemistry & Molecular Biology

AAV capsid design: A Goldilocks challenge

S. Zolotukhin et al.

Summary: In vivo therapeutic gene transfer is a novel class of medicines that relies on the safe and effective delivery of genetic material. The adeno-associated virus (AAV) vector has emerged as a preferred gene delivery vehicle, allowing for therapeutic gene expression in various clinical indications. Recent trends in AAV capsid engineering focus on enhancing targeting specificity, safety, and endurance, a significant challenge that is being addressed through techniques such as directed evolution, sequence analysis, and machine learning.

TRENDS IN MOLECULAR MEDICINE (2022)

Article Biotechnology & Applied Microbiology

Dose-Escalation Study of Systemically Delivered rAAVrh74.MHCK7.micro-dystrophin in the mdx Mouse Model of Duchenne Muscular Dystrophy

Rachael A. Potter et al.

Summary: Duchenne muscular dystrophy (DMD) is a rare, X-linked, fatal neuromuscular disease caused by mutations in the DMD gene, with interest in gene transfer therapy for treatment. A study showed that systemic delivery of a minidystrophin gene using an adeno-associated virus vector can potentially increase muscle strength and improve muscle tissue condition in DMD patients.

HUMAN GENE THERAPY (2021)

Review Biotechnology & Applied Microbiology

Current Clinical Applications of In Vivo Gene Therapy with AAVs

Jerry R. Mendell et al.

Summary: Hereditary diseases are caused by gene mutations, affecting millions of Americans, and gene therapy using adeno-associated virus (AAV) has shown promise in treating these diseases. Five treatments have been approved for commercialization, with many more in clinical trials, showcasing the potential of gene therapy in treating a wide range of genetic disorders.

MOLECULAR THERAPY (2021)

Article Biotechnology & Applied Microbiology

The clinical landscape for AAV gene therapies

Dmitry A. Kuzmin et al.

NATURE REVIEWS DRUG DISCOVERY (2021)

News Item Biotechnology & Applied Microbiology

Gene therapy community grapples with toxicity issues, as pipeline matures

Asher Mullard

Summary: Experts are calling for more transparency and better manufacturing standards for AAV-based candidates due to concerns of cancer, hepatotoxicity, haematological, and neurotoxicity.

NATURE REVIEWS DRUG DISCOVERY (2021)

Article Multidisciplinary Sciences

The membrane associated accessory protein is an adeno-associated viral egress factor

Zachary C. Elmore et al.

Summary: The membrane-associated accessory protein (MAAP) is identified as a novel viral egress factor that promotes the secretion of AAV serotypes. MAAP contains a cationic amphipathic domain critical for AAV secretion. Restoring MAAP expression can rescue the secretion defect in various AAV serotypes with mutated start sites.

NATURE COMMUNICATIONS (2021)

Article Biochemistry & Molecular Biology

Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species

Mohammadsharif Tabebordbar et al.

Summary: Evolved capsid variants of AAVs show enhanced potency and therapeutic efficacy for delivering genetic modifiers to muscle tissues, surpassing naturally occurring AAV capsids in mouse models of genetic muscle disease. These engineered vectors demonstrate conserved efficacy across different mouse strains, cynomolgus macaques, and human primary myotubes, indicating a promising approach for gene therapy.
Article Virology

Receptor Switching in Newly Evolved Adeno-associated Viruses

L. Patrick Havlik et al.

Summary: New AAV variants with enhanced cellular binding, uptake, and transduction have been evolved through infectious cycling, with one able to recognize sulfated glycosaminoglycans and another switching receptors from AAVR to integrin beta 1. The visualization of the AAVhum.8 capsid revealed a newly acquired integrin recognition motif, providing insights into designing viruses with improved attributes for gene therapy applications.

JOURNAL OF VIROLOGY (2021)

Review Genetics & Heredity

Engineering adeno-associated virus vectors for gene therapy

Chengwen Li et al.

NATURE REVIEWS GENETICS (2020)

Editorial Material Biotechnology & Applied Microbiology

Immunity to Cas9 as an Obstacle to Persistent Genome Editing

Veronica Gough et al.

MOLECULAR THERAPY (2020)

Editorial Material Biotechnology & Applied Microbiology

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

James M. Wilson et al.

HUMAN GENE THERAPY (2020)

Article Biotechnology & Applied Microbiology

Adeno-Associated Virus-Induced Dorsal Root Ganglion Pathology

Juliette Hordeaux et al.

HUMAN GENE THERAPY (2020)

Article Medicine, Research & Experimental

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

Zachary C. Elmore et al.

JCI INSIGHT (2020)

Article Multidisciplinary Sciences

Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants

Jonas Weinmann et al.

NATURE COMMUNICATIONS (2020)

Article Biochemistry & Molecular Biology

Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy

Christopher E. Nelson et al.

NATURE MEDICINE (2019)

Review Biotechnology & Applied Microbiology

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

Dan Wang et al.

NATURE REVIEWS DRUG DISCOVERY (2019)

Article Genetics & Heredity

Reduction of Autophagic Accumulation in Pompe Disease Mouse Model Following Gene Therapy

Angela L. McCall et al.

CURRENT GENE THERAPY (2019)

Article Biotechnology & Applied Microbiology

Mapping the Structural Determinants Required for AAVrh. 10 Transport across the Blood-Brain Barrier

Blake H. Albright et al.

MOLECULAR THERAPY (2018)

Letter Biotechnology & Applied Microbiology

The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL/6J Mice

Juliette Hordeaux et al.

MOLECULAR THERAPY (2018)

Article Medicine, Research & Experimental

AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice

Chady H. Hakim et al.

JCI INSIGHT (2018)

Article Medicine, General & Internal

Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy

J. R. Mendell et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Multidisciplinary Sciences

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

Longping Victor Tse et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

Article Multidisciplinary Sciences

Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy

Caroline Le Guiner et al.

NATURE COMMUNICATIONS (2017)

Article Multidisciplinary Sciences

In vivo gene editing in dystrophic mouse muscle and muscle stem cells

Mohammadsharif Tabebordbar et al.

SCIENCE (2016)

Article Biotechnology & Applied Microbiology

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

Sourav R. Choudhury et al.

MOLECULAR THERAPY (2016)

Article Biotechnology & Applied Microbiology

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

Benjamin E. Deverman et al.

NATURE BIOTECHNOLOGY (2016)

Article Biochemistry & Molecular Biology

Engraftment of a Galactose Receptor Footprint onto Adeno-associated Viral Capsids Improves Transduction Efficiency

Shen Shen et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2013)

Article Virology

Structural Insight into the Unique Properties of Adeno-Associated Virus Serotype 9

Michael A. DiMattia et al.

JOURNAL OF VIROLOGY (2012)

Article Biotechnology & Applied Microbiology

Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle

Aravind Asokan et al.

NATURE BIOTECHNOLOGY (2010)