Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9

Rajão‐Saraiva, Joana; Nobre, Rui Jorge; Almeida, Luís Pereira de

doi:10.1016/j.jconrel.2016.09.011

Cited by 154 publications

(132 citation statements)

References 135 publications

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“…Although rAAV2 belongs to the AAV2 serotype and may strongly bind heparan sulphate, our AAV9-derived retrograde AAV variant has the advantage of reduced binding to heparin sulfate (Shen et al, 2011) and therefore it is less affected by changes in brain extracellular matrix (e.g. due to neuroinflammation associated with neurodegeneration); AAV9 is only infrequently targeted by pre-existing immunity to AAVs (Zhang et al, 2011; Saraiva et al, 2016) and may provide the entry point to enhanced vectors for circuit-specific gene therapy in humans since AAV9 has been already successfully tested for this application (Boutin et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Commisso

Ding

Varadi

et al. 2018

eLife

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Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motoneurons in the primary motor cortex (pMO) and in spinal cord. However, the pathogenic process involves multiple subnetworks in the brain and functional MRI studies demonstrate an increase in functional connectivity in areas connected to pMO despite the ongoing neurodegeneration. The extent and the structural basis of the motor subnetwork remodeling in experimentally tractable models remain unclear. We have developed a new retrograde AAV9 to quantitatively map the projections to pMO in the SOD1(G93A) ALS mouse model. We show an increase in the number of neurons projecting from somatosensory cortex to pMO at presymptomatic stages, followed by an increase in projections from thalamus, auditory cortex and contralateral MO (inputs from 20 other structures remains unchanged) as disease advances. The stage- and structure-dependent remodeling of projection to pMO in ALS may provide insights into the hyperconnectivity observed in ALS patients.

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Section: Discussionmentioning

confidence: 99%

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Commisso

Ding

Varadi

et al. 2018

eLife

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“…First, the optimal injection route for AAV vector treatment needs to be determined. Systemically administered AAV9‐based vectors reportedly pass through the blood–brain barrier and can induce expression in the brain . Similarly, we have shown that intracardiac injection of an AAV9‐based vector resulted in the expression of GLUT1 in the murine brain .…”

Section: Discussionmentioning

confidence: 53%

Gene therapy for Glut1‐deficient mouse using an adeno‐associated virus vector with the human intrinsic GLUT1 promoter

Nakamura

Muramatsu

Takino

et al. 2018

The Journal of Gene Medicine

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“…One way to circumvent the problems inherent in protein or peptide delivery has been to use Adenoviral, AAV or lentiviral vectors as carriers for sequences encoding the therapeutic protein or peptide (e.g., Kim et al, 2004; Bourdenx et al, 2014; Parr-Brownlie et al, 2015; Blessing and Déglon, 2016; Saraiva et al, 2016). Vectors have been developed that will preferentially target neurons although most still require intracerebral inoculation.…”

Section: Fighting Fire With Fire: Do Amyloid Precursors Have Therapeumentioning

confidence: 99%

Transthyretin and BRICHOS: The Paradox of Amyloidogenic Proteins with Anti-Amyloidogenic Activity for Aβ in the Central Nervous System

Buxbaum

Johansson

2017

Front. Neurosci.

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Amyloid fibrils are physiologically insoluble biophysically specific β-sheet rich structures formed by the aggregation of misfolded proteins. In vivo tissue amyloid formation is responsible for more than 30 different disease states in humans and other mammals. One of these, Alzheimer's disease (AD), is the most common form of human dementia for which there is currently no definitive treatment. Amyloid fibril formation by the amyloid β-peptide (Aβ) is considered to be an underlying cause of AD, and strategies designed to reduce Aβ production and/or its toxic effects are being extensively investigated in both laboratory and clinical settings. Transthyretin (TTR) and proteins containing a BRICHOS domain are etiologically associated with specific amyloid diseases in the CNS and other organs. Nonetheless, it has been observed that TTR and BRICHOS structures are efficient inhibitors of Aβ fibril formation and toxicity in vitro and in vivo, raising the possibility that some amyloidogenic proteins, or their precursors, possess properties that may be harnessed for combating AD and other amyloidoses. Herein, we review properties of TTR and the BRICHOS domain and discuss how their abilities to interfere with amyloid formation may be employed in the development of novel treatments for AD.

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Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9

Cited by 154 publications

References 135 publications

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Gene therapy for Glut1‐deficient mouse using an adeno‐associated virus vector with the human intrinsic GLUT1 promoter

Transthyretin and BRICHOS: The Paradox of Amyloidogenic Proteins with Anti-Amyloidogenic Activity for Aβ in the Central Nervous System

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