Adeno-Associated Viral Vectors in Neuroscience Research

Haggerty, David L.; Grecco, Gregory G.; Reeves, Kaitlin C.; Atwood, Brady K.

doi:10.1016/j.omtm.2019.11.012

Cited by 91 publications

(69 citation statements)

References 169 publications

(406 reference statements)

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“…We overexpressed the TAC1 gene, which gives rise to multiple tachykinins products [reviewed here (Atanasova & Reznikov, 2018)]. While the AAV‐2.1 serotype used in this study has a natural tropism for neurons (Haggerty et al, 2020), other cells are likely to be transduced (Yan et al, 2013). Therefore, the TAC1 gene will be under cell‐type specific regulation.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway

et al. 2021

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Substance P (SP) is a tachykinin that regulates airway mucous secretion in both health and disease. Our study aimed to determine whether overexpression of SP without pre‐existing inflammation was sufficient to induce changes in mucin secretion and transport in small airways. Utilizing porcine precision‐cut lung slices, we measured the impact of AAV‐mediated overexpression of SP on airway physiology ex vivo. Immunofluorescence signal intensity for MUC5AC was significantly increased in SP‐overexpressed precision‐cut lung slices compared to GFP controls. No difference in MUC5B signal intensity between treatments was detected. SP‐overexpressed precision‐cut lung slices also exhibited decreased IL10 mRNA, an important inhibitor of mucous cell metaplasia. Overt deficits in mucociliary transport were not noted, though a trend for decreased mean transport speed was detected in methacholine‐challenged airways overexpressing SP compared to GFP controls. Pharmacologic inhibition of the NF‐kβ pathway abrogated the effects of overexpression of SP on both MUC5AC and IL10. Collectively, these data suggest that overexpression of SP in the absence of existing inflammation increases MUC5AC via activation of the NF‐kβ pathway. Thus, these data further highlight SP as a key driver of abnormal mucous secretion and underscore NF‐kβ signaling as a pathway of potential therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway

et al. 2021

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“…Several AAV clinical trials were already undergoing for Alzheimer’s disease, Parkinson’s disease, rheumatoid arthritis, etc. [ 120 ]. The serotype of AAV most widely used in clinical trial is AAV2 that work well in the CNS but with poor infection efficiency in DRG [ 121 , 122 ].…”

Section: Current Challenges To Manipulate On Drg In In Vivo Modelsmentioning

confidence: 99%

Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons

Yeh

Luo

Hsieh

et al. 2020

Cells

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Neuropathic pain exerts a global burden caused by the lesions in the somatosensory nerve system, including the central and peripheral nervous systems. The mechanisms of nerve injury-induced neuropathic pain involve multiple mechanisms, various signaling pathways, and molecules. Currently, poor efficacy is the major limitation of medications for treating neuropathic pain. Thus, understanding the detailed molecular mechanisms should shed light on the development of new therapeutic strategies for neuropathic pain. Several well-established in vivo pain models were used to investigate the detail mechanisms of peripheral neuropathic pain. Molecular mediators of pain are regulated differentially in various forms of neuropathic pain models; these regulators include purinergic receptors, transient receptor potential receptor channels, and voltage-gated sodium and calcium channels. Meanwhile, post-translational modification and transcriptional regulation are also altered in these pain models and have been reported to mediate several pain related molecules. In this review, we focus on molecular mechanisms and mediators of neuropathic pain with their corresponding transcriptional regulation and post-translational modification underlying peripheral sensitization in the dorsal root ganglia. Taken together, these molecular mediators and their modification and regulations provide excellent targets for neuropathic pain treatment.

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“…Ectopic gene overexpression mediated through viral vector delivery is a popular strategy to investigate neuronal gene regulation (Lentz et al, 2012;Haggerty et al, 2020). As previously described, numerous CRISPRa systems have been developed, enabling the potent activation of multiple genes in various tissues types.…”

Section: Regulating Transcription In Vivo With Dcas9mentioning

confidence: 99%

Genetically Engineering the Nervous System with CRISPR-Cas

Sandoval

Elahi

Ploski

2020

eNeuro

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The multitude of neuronal subtypes and extensive interconnectivity of the mammalian brain presents a substantial challenge to those seeking to decipher its functions. While the molecular mechanisms of several neuronal functions remain poorly characterized, advances in next-generation sequencing (NGS) and gene-editing technology have begun to close this gap. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (CRISPR-Cas) system has emerged as a powerful genetic tool capable of manipulating the genome of essentially any organism and cell type. This technology has advanced our understanding of complex neurologic diseases by enabling the rapid generation of novel, disease-relevant in vitro and transgenic animal models. In this review, we discuss recent developments in the rapidly accelerating field of CRISPR-mediated genome engineering. We begin with an overview of the canonical function of the CRISPR platform, followed by a functional review of its many adaptations, with an emphasis on its applications for

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Adeno-Associated Viral Vectors in Neuroscience Research

Cited by 91 publications

References 169 publications

Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway

Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway

Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons

Genetically Engineering the Nervous System with CRISPR-Cas

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