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Expert Opinion on Biological Therapy Sep 2022
Topics: Dependovirus; Genetic Vectors; Humans
PubMed: 35373689
DOI: 10.1080/14712598.2022.2060737 -
The Journal of Thoracic and... Dec 2022
Topics: Humans; Dependovirus; Genetic Vectors
PubMed: 34176616
DOI: 10.1016/j.jtcvs.2021.06.011 -
Human Gene Therapy Jun 2019Traditional gene therapy (gene replacement) has made a breakthrough in treating inherited diseases. Adeno-associated virus (AAV) has emerged as a highly promising vector... (Review)
Review
Traditional gene therapy (gene replacement) has made a breakthrough in treating inherited diseases. Adeno-associated virus (AAV) has emerged as a highly promising vector with innate ability, boosting the development of gene replacement and gene targeting. With the recent advance of engineered nucleases that work efficiently in human cells, AAV mediated-genome editing with nucleases has raised hopes for gene therapy of inherited and non-inherited diseases. Here, the applications of AAV-mediated genome editing are highlighted, and the prospect of AAV and nucleases that will render extension of such success in clinical gene therapy is discussed.
Topics: Animals; Dependovirus; Endonucleases; Gene Editing; Gene Expression Regulation, Viral; Genetic Vectors; Genome, Human; Genomics; Humans; Virus Integration
PubMed: 30588843
DOI: 10.1089/hum.2018.190 -
Proceedings of the National Academy of... Oct 1996Adeno-associated virus (AAV) has attracted considerable interest as a potential vector for gene delivery. Wild-type virus is notable for the lack of association with any... (Review)
Review
Adeno-associated virus (AAV) has attracted considerable interest as a potential vector for gene delivery. Wild-type virus is notable for the lack of association with any human disease and the ability to stably integrate its genome in a site-specific manner in a locus on human chromosome 19 (AAVS1). Use of a functional model system for AAV DNA integration into AAVS1 has allowed us to conclude that the recombination event is directed by cellular DNA sequences. Recombinant junctions isolated from our integration assay were analyzed and showed characteristics similar to those found in latently infected cell lines. The minimal DNA signals within AAVS1 required for targeted integration were identified and shown to contain functional motifs of the viral origin of replication. A replication mediated model of AAV DNA integration is proposed.
Topics: Base Sequence; Chromosomes, Human, Pair 19; DNA; DNA Replication; DNA, Viral; Dependovirus; Genetic Vectors; Humans; Models, Genetic; Molecular Sequence Data; Nucleic Acid Conformation; Recombination, Genetic; Virus Integration; Virus Replication
PubMed: 8876128
DOI: 10.1073/pnas.93.21.11288 -
Current Topics in Microbiology and... 1996
Review
Topics: Animals; Base Sequence; DNA, Viral; Dependovirus; Genetic Therapy; Genetic Vectors; Humans; Molecular Sequence Data; Parvoviridae Infections; Virus Latency; Virus Replication
PubMed: 8794242
DOI: 10.1007/978-3-642-80207-2_1 -
Communications Biology May 2023The adeno-associated virus (AAV) is a potent vector for in vivo gene transduction and local therapeutic applications of AAVs, such as for skin ulcers, are expected....
The adeno-associated virus (AAV) is a potent vector for in vivo gene transduction and local therapeutic applications of AAVs, such as for skin ulcers, are expected. Localization of gene expression is important for the safety and efficiency of genetic therapies. We hypothesized that gene expression could be localized by designing biomaterials using poly(ethylene glycol) (PEG) as a carrier. Here we show one of the designed PEG carriers effectively localized gene expression on the ulcer surface and reduced off-target effects in the deep skin layer and the liver, as a representative organ to assess distant off-target effects, using a mouse skin ulcer model. The dissolution dynamics resulted in localization of the AAV gene transduction. The designed PEG carrier may be useful for in vivo gene therapies using AAVs, especially for localized expression.
Topics: Polyethylene Glycols; Dependovirus; Genetic Vectors; Genetic Therapy; Biocompatible Materials
PubMed: 37193797
DOI: 10.1038/s42003-023-04851-w -
Biochimica Et Biophysica Acta Dec 1988
Review
Topics: Base Sequence; Cloning, Molecular; DNA Replication; DNA, Viral; Dependovirus; Gene Expression Regulation; Molecular Sequence Data; Simian virus 40; Virus Replication
PubMed: 2850017
DOI: 10.1016/0167-4781(88)90116-9 -
Molecular Therapy : the Journal of the... Jan 2014
Topics: Capsid; Dependovirus; Genetic Vectors; Humans; Virion
PubMed: 24384906
DOI: 10.1038/mt.2013.268 -
Clinical Microbiology Reviews Oct 2008The unique life cycle of adeno-associated virus (AAV) and its ability to infect both nondividing and dividing cells with persistent expression have made it an attractive... (Review)
Review
The unique life cycle of adeno-associated virus (AAV) and its ability to infect both nondividing and dividing cells with persistent expression have made it an attractive vector. An additional attractive feature of the wild-type virus is the lack of apparent pathogenicity. Gene transfer studies using AAV have shown significant progress at the level of animal models; clinical trials have been noteworthy with respect to the safety of AAV vectors. No proven efficacy has been observed, although in some instances, there have been promising observations. In this review, topics in AAV biology are supplemented with a section on AAV clinical trials with emphasis on the need for a deeper understanding of AAV biology and the development of efficient AAV vectors. In addition, several novel approaches and recent findings that promise to expand AAV's utility are discussed, especially in the context of combining gene therapy ex vivo with new advances in stem or progenitor cell biology.
Topics: Animals; Dependovirus; Genetic Therapy; Humans; Transduction, Genetic
PubMed: 18854481
DOI: 10.1128/CMR.00008-08 -
Molecular Therapy : the Journal of the... Jul 2008Recombinant adeno-associated virus (rAAV) holds promise as a gene therapy vector for a multitude of genetic disorders such as hemophilia, cystic fibrosis, and the... (Review)
Review
Recombinant adeno-associated virus (rAAV) holds promise as a gene therapy vector for a multitude of genetic disorders such as hemophilia, cystic fibrosis, and the muscular dystrophies. Given the variety of applications and tissue types toward which these vectors may be targeted, an understanding of rAAV transduction is crucial for the effective application of therapy. rAAV transduction mechanisms have been the subject of much study, resulting in a body of knowledge relating to events from virus-cell attachment through to vector genome conformation in the target cell nucleus. Instead of utilizing one mechanism in each phase of vector transduction, rAAV appears to employ multiple possible pathways toward transgene expression, in part dependent on rAAV serotype, dose, and target cell type. Once inside the nucleus, the rAAV genome exists in a predominantly episomal form; therefore, nondividing cells tend to be most stably transduced. However, rAAV has a low frequency of integration into the host cell genome, often in or near genes, and can be associated with host genome mutations. This review describes the current understanding of the mechanisms and rate-limiting steps involved in rAAV transduction.
Topics: Animals; DNA, Recombinant; Dependovirus; Genetic Therapy; Genetic Vectors; Humans; Mice; Transduction, Genetic; Virus Integration; Virus Internalization
PubMed: 18500252
DOI: 10.1038/mt.2008.103