Bat adeno-associated viruses as gene therapy vectors with the potential to evade human neutralizing antibodies

Wang, Yongdong; Li, Jialu; Liu, Yunbo; Z, Shi; Liu, Haizhou; Wei, Yuquan; Yang, Lin

doi:10.1038/s41434-019-0081-8

Cited by 16 publications

(12 citation statements)

References 35 publications

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“…Analysis of the BtAAV capsid structure using sequence analysis and cryo-EM revealed unique structural differences to human AAVs, including insertions and deletions in the capsid surface loops [ 221 ]. BtAAV capsids have been identified as possible vectors for gene therapy, as discussed later [ 221 , 222 ].…”

Section: Genus Dependoparvovirusmentioning

confidence: 99%

Small but mighty: old and new parvoviruses of veterinary significance

Jager

Tomlinson

Lopez-Astacio

et al. 2021

Virol J

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In line with the Latin expression “sed parva forti” meaning “small but mighty,” the family Parvoviridae contains many of the smallest known viruses, some of which result in fatal or debilitating infections. In recent years, advances in metagenomic viral discovery techniques have dramatically increased the identification of novel parvoviruses in both diseased and healthy individuals. While some of these discoveries have solved etiologic mysteries of well-described diseases in animals, many of the newly discovered parvoviruses appear to cause mild or no disease, or disease associations remain to be established. With the increased use of animal parvoviruses as vectors for gene therapy and oncolytic treatments in humans, it becomes all the more important to understand the diversity, pathogenic potential, and evolution of this diverse family of viruses. In this review, we discuss parvoviruses infecting vertebrate animals, with a special focus on pathogens of veterinary significance and viruses discovered within the last four years.

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Section: Genus Dependoparvovirusmentioning

confidence: 99%

Small but mighty: old and new parvoviruses of veterinary significance

Jager

Tomlinson

Lopez-Astacio

et al. 2021

Virol J

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“…Bats are a rich source of AAV genetic diversity [ 68 , 69 ] and may provide capsids with improved tropism and immune evasion properties. For example, bat AAV sequences have low capsid sequence identity (<60%), reduced antibody neutralization profiles, and increased muscle to liver transduction ratios compared to primate AAVs [ 70 ]. Bat AAV10HB was chosen for additional structural studies, and divergent loop structures were observed between AAV2, AAV5, and AAV10HB.…”

Section: Aav Capsid Modification Strategiesmentioning

confidence: 99%

Adeno-Associated Virus (AAV) Gene Delivery: Dissecting Molecular Interactions upon Cell Entry

Large

Silveria

Zane

et al. 2021

Viruses

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Human gene therapy has advanced from twentieth-century conception to twenty-first-century reality. The recombinant Adeno-Associated Virus (rAAV) is a major gene therapy vector. Research continues to improve rAAV safety and efficacy using a variety of AAV capsid modification strategies. Significant factors influencing rAAV transduction efficiency include neutralizing antibodies, attachment factor interactions and receptor binding. Advances in understanding the molecular interactions during rAAV cell entry combined with improved capsid modulation strategies will help guide the design and engineering of safer and more efficient rAAV gene therapy vectors.

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“…For example, synthetic variants obtained by structure-guided antigenic epitope evolution allows evading neutralizing antibodies (NAbs) [154]. Using an AAV capsid from other host species may also hide the virus from the pre-existing NAbs [155]. Empty capsids can act as bait for antibodies, promoting the distribution of the target vector [156].…”

Section: Viral Vectorsmentioning

confidence: 99%

Emerging Concepts and Challenges in Rheumatoid Arthritis Gene Therapy

et al. 2020

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Rheumatoid arthritis (RA) is a systemic inflammatory joint disease affecting about 1% of the population worldwide. Current treatment approaches do not ensure a cure for every patient. Moreover, classical regimens are based on nontargeted systemic immune suppression and have significant side effects. Biological treatment has advanced considerably but efficacy and specificity issues remain. Gene therapy is one of the potential future directions for RA therapy, which is rapidly developing. Several gene therapy trials done so far have been of moderate success, but experimental and genetics studies have yielded novel targets. As a result, the arsenal of gene therapy tools keeps growing. Currently, both viral and nonviral delivery systems are used for RA therapy. Herein, we review recent approaches for RA gene therapy.

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Bat adeno-associated viruses as gene therapy vectors with the potential to evade human neutralizing antibodies

Cited by 16 publications

References 35 publications

Small but mighty: old and new parvoviruses of veterinary significance

Small but mighty: old and new parvoviruses of veterinary significance

Adeno-Associated Virus (AAV) Gene Delivery: Dissecting Molecular Interactions upon Cell Entry

Emerging Concepts and Challenges in Rheumatoid Arthritis Gene Therapy

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