Systemic Delivery of Genes to Retina Using Adeno-Associated Viruses

Simpson, Chiab P.; Bolch, Susan; Zhu, Ping; Weidert, Frances; Dinculescu, Astra; Lobanova, Ekaterina S.

doi:10.1007/978-3-030-27378-1_18

Cited by 8 publications

(19 citation statements)

References 11 publications

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“…For example, the ability to systemically deliver an AAV vector with a particular cellular tropism or cellular promoter would be beneficial. The variants AAV9-PHP.B and PHP.eB have been reported to allow for significant transduction of the CNS following intravenous infusion but depending on the animal model or method of delivery used, different results are seen (Hordeaux et al, 2018;Simpson et al, 2019). While enhanced CNS tropism has been shown in a number of mouse strains including C57BL/6J mouse where it was first demonstrated, no such increase in transduction efficiency is seen in the BALB/cJ mouse strain (Hordeaux et al, 2018;Matsuzaki et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy

O’Carroll

Cook

Young

2021

Front. Mol. Neurosci.

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Different glial cell types are found throughout the central (CNS) and peripheral nervous system (PNS), where they have important functions. These cell types are also involved in nervous system pathology, playing roles in neurodegenerative disease and following trauma in the brain and spinal cord (astrocytes, microglia, oligodendrocytes), nerve degeneration and development of pain in peripheral nerves (Schwann cells, satellite cells), retinal diseases (Müller glia) and gut dysbiosis (enteric glia). These cell type have all been proposed as potential targets for treating these conditions. One approach to target these cell types is the use of gene therapy to modify gene expression. Adeno-associated virus (AAV) vectors have been shown to be safe and effective in targeting cells in the nervous system and have been used in a number of clinical trials. To date, a number of studies have tested the use of different AAV serotypes and cell-specific promoters to increase glial cell tropism and expression. However, true glial-cell specific targeting for a particular glial cell type remains elusive. This review provides an overview of research into developing glial specific gene therapy and discusses some of the issues that still need to be addressed to make glial cell gene therapy a clinical reality.

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Section: Discussionmentioning

confidence: 99%

AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy

O’Carroll

Cook

Young

2021

Front. Mol. Neurosci.

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“…Given that dorsal column axons showed such regeneration, we asked whether corticospinal axons, which are notoriously refractory to regeneration in the adult (Tuszynski and Steward, 2012), could show any sign of regeneration upon RhoA ablation. We therefore injected an AAV expressing tandem dimer (td) Tomato with or without AAV-Cre (Simpson et al, 2019) in the motor cortex of adult rhoA fl/fl mice and performed a dorsolateral hemisection at T12 2 weeks later and tissue clearing and 3D imaging analysis of the corticospinal tract 6 weeks after SCI (Figure 8B). As expected, RhoA deletion in adult corticospinal neurons did not stimulate their regeneration past the lesion site (Figures 8E and 8F).…”

Section: Articlementioning

confidence: 99%

RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury

Stern

Hilton

Burnside

et al. 2021

Neuron

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“…Using a rational design approach, novel variants of AAV2 and AAV5 have been generated, which demonstrate improved retinal transduction in non-human primate retina and tissue [72]. Moreover, novel AAV9-based capsids (AAV-PHP.eB) have been designed that can cross the blood-retinal barrier when delivered systemically [73].…”

Section: Viral Vectorsmentioning

confidence: 99%

The Ocular Gene Delivery Landscape

2021

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The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

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Systemic Delivery of Genes to Retina Using Adeno-Associated Viruses

Cited by 8 publications

References 11 publications

AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy

AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy

RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury

The Ocular Gene Delivery Landscape

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