Adeno-associated Virus Type 5 Reduces Learning Deficits and Restores Glutamate Receptor Subunit Levels in MPS VII Mice CNS

Liu, Gumei; He, Xiaohua; Martins, Inês; Heth, Jason; Chiorini, John A.; Davidson, Beverly L.

doi:10.1038/sj.mt.6300016

Cited by 30 publications

(22 citation statements)

References 38 publications

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“…This is consistent with the findings of Lubansu et al where AAV serotype 5 was shown to be ineffective in transducing rat embryonic (E15) ganglionic eminence cultures. These data are in contrast to studies showing that AAV serotype 5 was efficient at transducing cells in adult mouse 31,32 and non-human primate brain. 33,34 This discrepancy suggests that the availability of AAV5-binding sites, such as 2,3-linked sialic acid, 35 and potential receptors may vary from gestation through to adulthood.…”

Section: Discussioncontrasting

confidence: 99%

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

et al. 2011

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The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development.

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Section: Discussioncontrasting

confidence: 99%

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

et al. 2011

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“…These are limited as therapeutic agents cannot cross the BBB. Thus, the clinical severity including neuropsychiatric symptoms and the lack of efficient therapy led to trials of gene therapy (ex vivo and in vivo) and development of stem cell and encapsulation cell therapeutic approaches for disease [59][60][61][62]. Injections of recombinant virus vectors for systemic and CNS malfunctions directly into the brain have bypassed the BBB but the possibilities for tumor formation and toxicity could limit their development and use.…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Kabanov

Gendelman

2007

Progress in Polymer Science

243

138

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Neurodegenerative and infectious disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population's age. Alzheimer's disease alone currently affects 4.5 million Americans, and more than $100 billion is spent per year on medical and institutional care for affected people. Such numbers will double in the ensuing decades. Currently disease diagnosis for all disorders is made, in large measure, on clinical grounds as laboratory and neuroimaging tests confirm what is seen by more routine examination. Achieving early diagnosis would enable improved disease outcomes. Drugs, vaccines or regenerative proteins present "real" possibilities for positively affecting disease outcomes, but are limited in that their entry into the brain is commonly restricted across the blood-brain barrier. This review highlights how these obstacles can be overcome by polymer science and nanotechnology. Such approaches may improve diagnostic and therapeutic outcomes. New developments in polymer science coupled with cell-based delivery strategies support the notion that diseases that now have limited therapeutic options can show improved outcomes by advances in nanomedicine.

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“…Recombinant AAVs are being investigated as vectors for clinical gene transfer to a wide variety of cells and tissues (Hasbrouck and High, 2008; Kota et al, 2009; Maguire et al, 2009; Maguire et al, 2010; Muzyczka, 1992; Srivastava, 2008; Wagner et al, 1999). Transduction with AAV vectors has been shown to result in long-term transgene expression in vivo in several cell types including skeletal muscle, photoreceptors, liver, and neuronal cells (Daya and Berns, 2008; Hasbrouck and High, 2008; Liu et al, 2007). As a result, AAV was used in the first regulatory approval of a gene therapy product in Western nations, in 2012 within the European Union.…”

Section: Introductionmentioning

confidence: 99%

A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line

Wooley

Sharma

Weinstein

et al. 2017

Journal of Virological Methods

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A directed evolution approach was used to select for Adeno-associated virus (AAV) capsids that would exhibit more tropism toward an HIV-1 producer T cell line with the long-term goal of developing improved gene transfer vectors. A library of AAV variants was used to infect H9 T cells previously infected or uninfected by HIV-1 followed by AAV amplification with wild-type adenovirus. Six rounds of biological selection were performed, including negative selection and diversification after round three. The H9 T cells were successfully infected with all three wild-type viruses (AAV, adenovirus, and HIV-1). Four AAV cap mutants best representing the small number of variants emerging after six rounds of selection were chosen for further study. These mutant capsids were used to package an AAV vector and subsequently used to infect H9 cells that were previously infected or uninfected by HIV-1. A quantitative polymerase chain reaction assay was performed to measure cell-associated AAV genomes. Two of the four cap mutants showed a significant increase in the amount of cell-associated genomes as compared to wild-type AAV2. This study shows that directed evolution can be performed successfully to select for mutants with improved tropism for a T cell line in the presence of HIV-1.

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Adeno-associated Virus Type 5 Reduces Learning Deficits and Restores Glutamate Receptor Subunit Levels in MPS VII Mice CNS

Cited by 30 publications

References 38 publications

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line

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