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The Journal of Clinical Investigation Oct 1994
Review
Topics: Animals; Dependovirus; Genetic Therapy; Genetic Vectors; Humans
PubMed: 7929808
DOI: 10.1172/JCI117468 -
Methods in Enzymology 2012Adeno-associated virus (AAV) has emerged as an attractive vector for gene therapy. The benefits of using AAV for gene therapy include long-term gene expression, the... (Review)
Review
Adeno-associated virus (AAV) has emerged as an attractive vector for gene therapy. The benefits of using AAV for gene therapy include long-term gene expression, the inability to autonomously replicate without a helper virus, transduction of dividing and nondividing cells, and the lack of pathogenicity from wild-type infections. A number of Phase I and Phase II clinical trials utilizing AAV have been carried out worldwide (Aucoin et al., 2008; Mueller and Flotte, 2008). A number of challenges have been identified based upon data generated from these clinical trials. These challenges include (1) large scale manufacturing technologies in accordance with current Good Manufacturing Practices (cGMP), (2) tissue specific tropism of AAV vectors, (3) high-quality/high potency recombinant AAV vectors (rAAV), and (4) immune response to AAV capsids and transgene. In this chapter, we will provide an overview of AAV biology, AAV vectorology, rAAV manufacturing, and the current status on the latest rAAV clinical trials.
Topics: Cell Culture Techniques; Clinical Trials as Topic; Dependovirus; Gene Library; Genetic Therapy; Genetic Vectors; Genome, Viral; Hemophilia B; Humans; Leber Congenital Amaurosis; Technology, Pharmaceutical
PubMed: 22365777
DOI: 10.1016/B978-0-12-386509-0.00012-0 -
Molecular Therapy : the Journal of the... Mar 2016In addition to their broad potential for therapeutic gene delivery, adeno-associated virus (AAV) vectors possess the innate ability to stimulate homologous recombination... (Review)
Review
In addition to their broad potential for therapeutic gene delivery, adeno-associated virus (AAV) vectors possess the innate ability to stimulate homologous recombination in mammalian cells at high efficiencies. This process--referred to as AAV-mediated gene targeting--has enabled the introduction of a diverse array of genomic modifications both in vitro and in vivo. With the recent emergence of targeted nucleases, AAV-mediated genome engineering is poised for clinical translation. Here, we review key properties of AAV vectors that underscore its unique utility in genome editing. We highlight the broad range of genome engineering applications facilitated by this technology and discuss the strong potential for unifying AAV with targeted nucleases for next-generation gene therapy.
Topics: Animals; Dependovirus; Endonucleases; Gene Editing; Gene Targeting; Gene Transfer Techniques; Genetic Engineering; Genetic Vectors; Genome; Genomics; Humans; Research; Virus Integration
PubMed: 26373345
DOI: 10.1038/mt.2015.151 -
Contributions To Microbiology 2000
Review
Topics: Animals; DNA Replication; DNA, Viral; Dependovirus; Genome, Viral; Humans; Molecular Biology; Transcription, Genetic
PubMed: 10941571
DOI: 10.1159/000060327 -
Clinical and Translational Medicine Mar 2024Adeno-associated virus (AAV)-based therapies are recognized as one of the most potent next-generation treatments for inherited and genetic diseases. However, several... (Review)
Review
Adeno-associated virus (AAV)-based therapies are recognized as one of the most potent next-generation treatments for inherited and genetic diseases. However, several biological and technological aspects of AAV vectors remain a critical issue for their widespread clinical application. Among them, the limited capacity of the AAV genome significantly hinders the development of AAV-based gene therapy. In this context, genetically modified transgenes compatible with AAV are opening up new opportunities for unlimited gene therapies for many genetic disorders. Recent advances in de novo protein design and remodelling are paving the way for new, more efficient and targeted gene therapeutics. Using computational and genetic tools, AAV expression cassette and transgenic DNA can be split, miniaturized, shuffled or created from scratch to mediate efficient gene transfer into targeted cells. In this review, we highlight recent advances in AAV-based gene therapy with a focus on its use in translational research. We summarize recent research and development in gene therapy, with an emphasis on large transgenes (>4.8 kb) and optimizing strategies applied by biomedical companies in the research pipeline. We critically discuss the prospects for AAV-based treatment and some emerging challenges. We anticipate that the continued development of novel computational tools will lead to rapid advances in basic gene therapy research and translational studies.
Topics: Dependovirus; Transgenes; Genetic Therapy; Genetic Vectors
PubMed: 38488469
DOI: 10.1002/ctm2.1607 -
Science (New York, N.Y.) Jul 2022Two viruses plus a child's genetic background may explain a recent surge in the United Kingdom.
Two viruses plus a child's genetic background may explain a recent surge in the United Kingdom.
Topics: Child; Dependovirus; HLA Antigens; Hepatitis, Viral, Human; Humans; United Kingdom
PubMed: 35901143
DOI: 10.1126/science.ade1298 -
Molecular Therapy : the Journal of the... Jan 2022
Topics: CRISPR-Cas Systems; Dependovirus; Gene Editing; Lung
PubMed: 34895514
DOI: 10.1016/j.ymthe.2021.12.003 -
Current Opinion in Virology Dec 2016Viral replication by acquisition of the host cell biology represents a central part of a virus life cycle. Thereby, integration into the host genome constitutes a... (Review)
Review
Viral replication by acquisition of the host cell biology represents a central part of a virus life cycle. Thereby, integration into the host genome constitutes a successful strategy to ensure viral persistence and viruses have developed different mechanisms to integrate and benefit from cell's transcriptional and translational machinery. While lentiviral (e.g. HIV) integration is influenced by the chromatin landscape encountered upon nuclear entry, certain parvoviruses (e.g. AAV) integrate specifically within genomic regions bearing increasingly known sequence motifs. Gene therapy exploits these viral persistence strategies to achieve efficient and safe long-term transgene expression. Here we focus on two widely used vectors and their parental viruses, HIV and AAV, to discuss recent insights into lentiviral vector oncogenicity by alteration of endogenous transcripts as well as the unresolved AAV vectors genotoxic potential.
Topics: Animals; Carcinogenesis; DNA Damage; Dependovirus; Genetic Vectors; HIV; Host-Pathogen Interactions; Humans; Virus Integration
PubMed: 27474966
DOI: 10.1016/j.coviro.2016.07.004 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2011Adeno-associated virus is a kind of DNA defective parvovirus which is non-pathogenic. Recombinant-adeno-associated virus vector comes from wild-type non-pathogenic... (Review)
Review
Adeno-associated virus is a kind of DNA defective parvovirus which is non-pathogenic. Recombinant-adeno-associated virus vector comes from wild-type non-pathogenic adeno-associated virus and is highly secure, and it also has the advantages of broad host range. Recombinant-adeno-associated virus vector has become a hot spot for gene therapy and is widely used in gene therapy for cardiovascular diseases, especially for hypertension, heart failure, arteriosclerosis, and myocardial infarction.
Topics: Arteriosclerosis; Cardiovascular Diseases; Dependovirus; Genetic Therapy; Genetic Vectors; Heart Failure; Humans; Hypertension; Recombinant Proteins
PubMed: 21368431
DOI: 10.3969/j.issn.1672-7347.2011.02.016 -
Methods in Molecular Biology (Clifton,... 2019Adeno-associated virus (AAV) is an increasingly popular tool in the research laboratory, and use of this viral vector clinically is occurring at an accelerated pace....
Adeno-associated virus (AAV) is an increasingly popular tool in the research laboratory, and use of this viral vector clinically is occurring at an accelerated pace. Nevertheless, despite its popularity, AAV is a relatively cumbersome virus to produce; however, significant efforts have been invested to develop, optimize, and simplify methodology that allows the generation of high-quality AAV with significantly increased production yields. Here we describe multiple modalities for production and purification of AAV particles produced in HEK293 cell cultures using an iodixanol density gradient. We include two methods adapted for harvesting virus from the culture media: tangential flow filtration (TFF) and polyethylene glycol precipitation (PEGylation). Moreover, we also describe the protocol for anion exchange chromatography, which can be used after the iodixanol gradient as an additional purification step. Last, we provide various protocols for determining virus titer.
Topics: Chemical Precipitation; Dependovirus; Filtration; Genetic Therapy; Genetic Vectors; HEK293 Cells; Humans; Virus Cultivation
PubMed: 30706392
DOI: 10.1007/978-1-4939-9065-8_6