Site-specific integration by adeno-associated virus.

Linden, R. J.; Ward, Peter; Giraud, Catherine; Winocour, Ernest; Berns, Kenneth I.

doi:10.1073/pnas.93.21.11288

Cited by 744 publications

(229 citation statements)

References 49 publications

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“…First, the ability of AAV to transduce multiple tissues such as liver, heart and brain in vivo results in localized production of GUSB in many organs, which can then locally or distantly cross-correct uninfected cells. Second, the persistence of the recombinant AAV genome as either stable episomes or integrated forms 19,20 provides long-term GUSB expression throughout development. Finally, the low immunogenicity of recombinant AAV vectors 21,22 make this virus a potentially acceptable option for neonatal use.…”

Section: Discussionmentioning

confidence: 99%

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

et al. 2001

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Section: Discussionmentioning

confidence: 99%

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

et al. 2001

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“…In the absence of such a helper virus, AAV integrates into the host chromosome, usually chromosome 19. 2 The ability of AAV to establish a latent infection without causing disease or pathology makes it a good candidate for a gene therapy viral transduction vector. AAV is a nonenveloped virus with a single-stranded linear DNA genome of 4680 bp.…”

Section: Introductionmentioning

confidence: 99%

Transfer of activation-dependent gene expression into T cell lines by recombinant adeno-associated virus

Zhang

Fuleihan

1999

Gene Ther

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We examined the ability of recombinant adeno-associated no detectable constitutive expression of luciferase and that virus (rAAV) to transfer regulated gene expression into T luciferase gene expression remained inducible for at least cell lines. An AAV-based vector containing the neomycin 180 days. Luciferase expression was activated by PMA resistance gene and expressing the firefly luciferase (luc) and ionomycin and by anti-CD3 antibodies and was gene under the regulatory control of the interleukin 2 proinhibited by cyclosporin A. Examination of G418-resistant moter (pAAV-luc) was generated and adenovirus-free clones showed that rAAV-luc had integrated into the host rAAV (rAAV-luc) was produced from this vector. Transfecchromosomes but that some of the clones lost some of tion of pAAV-luc into the human T cell line Jurkat resulted the transferred DNA or lost expression from the transferred in luciferase expression while infection of Jurkat T cells DNA. These results indicate that rAAV can transfer and with rAAV-luc resulted in significant luciferase expression integrate regulated gene expression into T cell lines but only after selection for neomycin-resistant cells. Long-term that the transferred genetic material may be lost or its growth of transduced Jurkat T cells showed that there was expression may be silenced over time.

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“…In addition, AAV integrates into a specific site on chromosome 19, permitting increased DNA stability and prolonged expression time. 2 Minor disadvantages include lower viral titers than those obtained with adenovirus and small insert size; the latter is generally not an issue for most currently known candidate therapeutic genes for PD. Recent studies using several vectors derived from AAV serotypes (e.g., AAV1, -4, -5, and -6) have improved potency and broadened tropism.…”

Section: Gene Therapy For Parkinson's Disease (Pd)mentioning

confidence: 99%

Advances in Gene Therapy for Movement Disorders

Mochizuki

Yasuda

Mouradian³

2008

Neurotherapeutics

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Summary:After nearly 20 years of preclinical experimentation with various gene delivery approaches in animal models of Parkinson's disease (PD), clinical trials are finally underway. The risk/benefit ratio for these procedures is now generally considered acceptable under approved protocols. The current vehicle for gene delivery to the human brain is recombinant adeno-associated viral vector, which is nonpathogenic and non-self-amplifying. Candidate genes tested in PD patients encode 1) glutamic acid decarboxylase, which is injected into the subthalamic nucleus to catalyze biosynthesis of the inhibitory neurotransmitter ␥-aminobutyric acid and so essentially mimic deep brain stimulation of this nucleus; 2) aromatic Lamino acid decarboxylase, which converts L-dopa to dopamine; and 3) neurturin, a member of the glial cell line-derived neurotrophic factor family. Unraveling the genetic underpinnings of PD could allow gene therapy to go beyond modulating neurotransmission or providing trophic effects to dopaminergic neurons by delivering a specific missing or defective gene. For example, the parkin gene (PARK2) is linked to recessively inherited PD due to loss of function mutations; it prevents ␣-synuclein-induced degeneration of nigral dopaminergic neurons in rats and nonhuman primates. On the other hand, for dominantly inherited Huntington's disease (HD), in which an expanded polyglutamine tract imparts to the protein huntingtin a toxic gain of function, repressing expression of the mutant allele in the striatum using RNA interference technology mitigates pathology and delays the phenotype in a mouse model. Here we review the current state of preclinical and clinical gene therapy studies conducted in PD and HD.

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Site-specific integration by adeno-associated virus.

Cited by 744 publications

References 49 publications

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

Transfer of activation-dependent gene expression into T cell lines by recombinant adeno-associated virus

Advances in Gene Therapy for Movement Disorders

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