Recombinant Viral Vectors as Neuroscience Tools

Chen, Shih‐Heng; Haam, Juhee; Walker, Mitzie; Scappini, Erica; Naughton, John; Martin, Negin P.

doi:10.1002/cpns.67

Cited by 30 publications

(22 citation statements)

References 59 publications

(83 reference statements)

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“…Another promising approach lies in gene therapy using non-replicating viral vectors such as gene delivery forms of adeno-associated virus (AAVs), retro and lentiviruses (Lundberg et al, 2008), and glycoprotein-deleted rabies virus (Chen et al, 2019;Wang F. et al, 2019;Wang X. et al, 2019;. Gene delivery using AAVs has the advantage in that these viruses do not integrate into host chromosomes yet persist as episomic chromosomes that do not provoke insertional mutations and permit stable gene expression in neuronal and glial cells (Penaud-Budloo et al, 2008).…”

Section: Viral Vectorsmentioning

confidence: 99%

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Iarkov

Barreto

Grizzell

et al. 2020

Front. Aging Neurosci.

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Parkinson's disease (PD) is the second-leading cause of dementia and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra alongside the presence of intraneuronal α-synuclein-positive inclusions. Therapies to date have been directed to the restoration of the dopaminergic system, and the prevention of dopaminergic neuronal cell death in the midbrain. This review discusses the physiological mechanisms involved in PD as well as new and prospective therapies for the disease. The current data suggest that prevention or early treatment of PD may be the most effective therapeutic strategy. New advances in the understanding of the underlying mechanisms of PD predict the development of more personalized and integral therapies in the years to come. Thus, the development of more reliable biomarkers at asymptomatic stages of the disease, and the use of genetic profiling of patients will surely permit a more effective treatment of PD.

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Section: Viral Vectorsmentioning

confidence: 99%

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Iarkov

Barreto

Grizzell

et al. 2020

Front. Aging Neurosci.

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“…Viral vectors, particularly those that permit efficient gene transfer to the central nervous system (CNS) from axonal terminals or across the blood-brain barrier, are useful to analyse the structure and function of specific neuronal circuits around the injection site [1][2][3][4][5][6][7][8][9][10][11] and have become one of the most promising therapy tools to deliver therapeutic genes to a distant target area [5,12]. Compared with traditional retrograde tracers, viral vectors can express genes in specific neuron groups [9,13] and have been widely used to monitor and manipulate neuronal activities by expressing optogenetic [14,15], chemogenetic [16,17] and calcium-sensitive functional probes [18][19][20]. Some natural and engineered neurotropic viruses exhibit retrograde infection capabilities, such as the pseudorabies virus (PRV) [21], herpes simplex virus (HSV) [22], rabies virus (RABV) [13,23], lentivirus (LV) [24][25][26][27], canine adenovirus (CAV) [6,28], and adeno-associated virus (AAV) [5,[29][30][31].…”

Section: Introductionmentioning

confidence: 99%

AAV9-Retro mediates efficient transduction with axon terminal absorption and blood–brain barrier transportation

Kuang

Zhong

et al. 2020

Mol Brain

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Recombinant adeno-associated viruses (rAAVs), particularly those that permit efficient gene transfer to neurons from axonal terminals or across the blood–brain barrier, are useful vehicles for structural and functional studies of the neural circuit and for the treatment of many gene-deficient brain diseases that need to compensate for the correct genes in every cell in the whole brain. However, AAVs with these two advantages have not been reported. Here, we describe a new capsid engineering method, which exploits the combination of different capsids and aims to yield a capsid that can provide more alternative routes of administration that are more suitable for the wide-scale transduction of the central nervous system (CNS). A new AAV variant, AAV9-Retro, was developed by inserting the 10-mer peptide fragment from AAV2-Retro into the capsid of AAV9, and the biodistribution properties were evaluated in mice. By intracranial and intravenous injection in the mice, we found that AAV9-Retro can retrogradely infect projection neurons with an efficiency comparable to that of AAV2-Retro and retains the characteristic of AAV9, which can be transported across the nervous system. Our strategy provides a new tool for the manipulation of neural circuits and future preclinical and clinical treatment of some neurological and neurodegenerative disorders.

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“…Viral vectors, especially which permit e cient gene transfer to central nervous system (CNS) from axonal terminals or across the blood-brain barrier, are useful for analyzing structure and function of speci c neuronal circuits around the injection site [1][2][3][4][5][6][7][8][9][10][11], and have become one of the most potential and promising therapy tools by delivery therapeutic genes to a distant target area [5,12]. Compared with traditional retrograde tracers, viral vectors can express genes in speci c neuron groups [9,13], and have been widely used to monitor and manipulate neuronal activities by expressing optogenetic [14,15], chemogenetic [16,17] and calcium-sensitive functional probes [18][19][20]. Some natural and engineered neurotropic viruses exhibit retrograde infection capabilities, including pseudorabies virus (PRV) [21], herpes simplex virus (HSV) [22], rabies virus (RABV) [13,23], lentivirus (LV) [24][25][26][27], canine adenovirus (CAV) [6,28], and adeno-associated virus (AAV) [5,[29][30][31], etc.…”

Section: Introductionmentioning

confidence: 99%

AAV9-Retro Mediates Efficient Transduction with Axon Terminal Absorption and Blood-brain Barrier Transportation

Lin

Zhong

et al. 2020

Preprint

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Recombinant adeno-associated viruses (rAAVs), especially which permit efficient gene transfer to neurons from axonal terminals or across the blood-brain barrier, are useful vehicles for the structural and functional studies of neural circuit, and for the treatment of many gene-deficient brain diseases that needs to compensate for the correct genes to every cell in the whole brain. However, AAVs with these two advantages have not been reported. Here, we describe a new capsid engineering method, which draws on advantage combination of different capsids, and aims to yield a capsid that can provide more alternative routes of administration, which are more suitable for wide-scale transduction of the CNS. A new AAV variant, AAV9-Retro, was developed by inserting the 10-mer peptide fragment from AAV2-Retro into the capsid of AAV9, and the biodistribution properties were evaluated in mice. By intracranial and intravenous injection in the mice, we found that AAV9-Retro can retrogradely infect projection neurons with efficiency comparable to AAV2-Retro, and retains the characteristic of AAV9 that can transport across the nervous system. Our strategy provides a new tool for the manipulation of neural circuits, and for the future preclinical and clinical treatment of some neurological and neurodegenerative disorders.

show abstract

Recombinant Viral Vectors as Neuroscience Tools

Cited by 30 publications

References 59 publications

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine

AAV9-Retro mediates efficient transduction with axon terminal absorption and blood–brain barrier transportation

AAV9-Retro Mediates Efficient Transduction with Axon Terminal Absorption and Blood-brain Barrier Transportation

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