Downregulating the P2X3 receptor in the carotid body to reduce blood pressure via acoustic gene delivery in canines

Xue, Qiao; Wang, Ruiyu; Wang, Liang; Xiong, Bin; Li, Lingjiao; Qian, Jun; Lu, Hao; Wang, Zhigang; Liu, Dichuan; Deng, Changming; Shu, Rong; Yao, Yuanqing; Jiang, Yonghong; Zhu, Qingsan; Jing, Huang

doi:10.1016/j.trsl.2020.06.005

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…Thus, analysis of which P2X receptors are present in the vagal afferent nerve terminals of dogs is required to support these findings. P2X3 mRNA and protein has been detected in carotid body of dogs, with its knockdown shown to reduce blood pressure (Xue, et al, 2021), as first shown in rats (Pijacka, et al, 2016). To the best of our knowledge, this provides the first report of the targeting a specific P2X receptor in dogs to alter physiological or pathophysiological processes and supports the therapeutic potential of targeting these receptors in veterinary medicine.…”

Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 56%

P2X receptors: Insights from the study of the domestic dog

2023

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Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 56%

P2X receptors: Insights from the study of the domestic dog

2023

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“…For example, Xue et al could reduce the mRNA and protein expression in the CB by targeted chromosomal DNA cleavage using CRISPR/Cas9-containing cationic microbubbles in a canine model, ultimately leading to lower blood pressure. However, the in vitro transfection efficiency was not as high as expected . Since ultrasound delivery can be based on temperature regulation, the mechanism of these carriers is similar to that of heat-responsive systems.…”

Section: Ultrasound-responsive Systems For Gene Editingmentioning

confidence: 75%

“…However, the in vitro transfection efficiency was not as high as expected. 117 Since ultrasound delivery can be based on temperature regulation, the mechanism of these carriers is similar to that of heat-responsive systems. Hence, the polymers that undergo degradation in response to heat can also be combined with drug or gene delivery systems.…”

Section: Ultrasound-responsive Systems For Genementioning

confidence: 99%

Smart Strategies for Precise Delivery of CRISPR/Cas9 in Genome Editing

Hasanzadeh

Noori

Jahandideh

et al. 2022

ACS Appl. Bio Mater.

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The emergence of CRISPR/Cas technology has enabled scientists to precisely edit genomic DNA sequences. This approach can be used to modulate gene expression for the treatment of genetic disorders and incurable diseases such as cancer. This potent genome-editing tool is based on a single guide RNA (sgRNA) strand that recognizes the targeted DNA, plus a Cas nuclease protein for binding and processing the target. CRISPR/Cas has great potential for editing many genes in different types of cells and organisms both in vitro and in vivo. Despite these remarkable advances, the risk of off-target effects has hindered the translation of CRISPR/Cas technology into clinical applications. To overcome this hurdle, researchers have devised gene regulatory systems that can be controlled in a spatiotemporal manner, by designing special sgRNA, Cas, and CRISPR/Cas delivery vehicles that are responsive to different stimuli, such as temperature, light, magnetic fields, ultrasound (US), pH, redox, and enzymatic activity. These systems can even respond to dual or multiple stimuli simultaneously, thereby providing superior spatial and temporal control over CRISPR/Cas gene editing. Herein, we summarize the latest advances on smart sgRNA, Cas, and CRISPR/Cas nanocarriers, categorized according to their stimulus type (physical, chemical, or biological).

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“…More recently, canine models with P2X3R deficiency on CBs were created. This model showed a decreased BP and normalized the sympatho-vagal balance [ 101 ], thus suggesting the importance of P2X3R in CBs to control BP and sympathetic activity.…”

Section: Purinoceptors In the Regulation Of Blood Pressurementioning

confidence: 99%

Purinoceptor: a novel target for hypertension

Zhu

et al. 2022

Purinergic Signalling

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Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. A1R, A2AR, A2BR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.

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Downregulating the P2X3 receptor in the carotid body to reduce blood pressure via acoustic gene delivery in canines

Cited by 5 publications

References 34 publications

P2X receptors: Insights from the study of the domestic dog

P2X receptors: Insights from the study of the domestic dog

Smart Strategies for Precise Delivery of CRISPR/Cas9 in Genome Editing

Purinoceptor: a novel target for hypertension

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