rAAV-miniBEND: A targeted vector for brain endothelial cell gene delivery and cerebrovascular malformation modeling Article Swipe

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Jun-Liszt Li , Zhanying Bi , Xing-jun Chen , Tianyue Ming , Baoshan Qiu , Fengzhi Li , Ziyan Feng , Daosheng Ai , Tingting Zhang , Jiayu Wang , Shuai Lin , Yiping Lu , Zhen Wang , Juan Huang , Fei Zhao , Hu Zhao , Yilong Wang , Wenzhi Sun , Woo‐Ping Ge ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1101/2025.06.10.658979

Defects in brain endothelial cells (brainECs) can cause severe cerebrovascular malformations, including arteriovenous malformation (AVM) and cerebral cavernous malformation (CCM). The lack of appropriate tools for cerebrovascular disease modeling and local genetic manipulation of the brain vasculature hinders research on cerebrovascular malformations. Here we develop a recombinant adeno-associated virus (rAAV) tool miniBEND (rAAV-based mini -system for b rain end othelial cells, rAAV-miniBEND), which combines a minimal promoter and an optimized cis-acting element (cis-element) isolated from the mouse gene Tek . This system achieves gene expression specifically in mouse and rat brainECs. Using rAAV-miniBEND, we achieve high-efficiency and high-specificity gene expression in brainECs through intracranial injection at various developmental stages and through intravenous administration at all postnatal stages in mice. Furthermore, we use rAAV-miniBEND to model sporadic CCMs mediated by MAP3K3 I441M and AVMs mediated by Braf V600E . We demonstrate that somatic expression of Braf V600E in brainECs induces an AVM phenotype, and that brainEC proliferation are important for AVM development. Thus, our rAAV-miniBEND system provides a valuable and widely applicable tool for cerebrovascular disease modeling and local or global brainEC gene delivery.

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Vector (molecular biology) Gene delivery Genetic enhancement Gene Medicine Biology Genetics Recombinant DNA

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2025.06.10.658979
OA Status: green
Cited By: 1
References: 85
Related Works: 10
OpenAlex ID: https://openalex.org/W4411323583

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DOI: https://doi.org/10.1101/2025.06.10.658979

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Title: rAAV-miniBEND: A targeted vector for brain endothelial cell gene delivery and cerebrovascular malformation modeling

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-06-15

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Authors: Jun-Liszt Li, Zhanying Bi, Xing-jun Chen, Tianyue Ming, Baoshan Qiu, Fengzhi Li, Ziyan Feng, Daosheng Ai, Tingting Zhang, Jiayu Wang, Shuai Lin, Yiping Lu, Zhen Wang, Juan Huang, Fei Zhao, Hu Zhao, Yilong Wang, Wenzhi Sun, Woo‐Ping Ge

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Landing page: https://doi.org/10.1101/2025.06.10.658979

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Concepts: Vector (molecular biology), Gene delivery, Genetic enhancement, Gene, Medicine, Biology, Genetics, Recombinant DNA

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Cited by: 1

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abstract_inverted_index.mini	54
abstract_inverted_index.rain	58
abstract_inverted_index.that	141, 154
abstract_inverted_index.tool	51, 172
abstract_inverted_index.(AVM)	15
abstract_inverted_index.I441M	131
abstract_inverted_index.Thus,	162
abstract_inverted_index.Using	92
abstract_inverted_index.V600E	137, 146
abstract_inverted_index.brain	3, 36
abstract_inverted_index.cause	8
abstract_inverted_index.cells	5
abstract_inverted_index.local	31, 178
abstract_inverted_index.mice.	119
abstract_inverted_index.model	125
abstract_inverted_index.mouse	77, 88
abstract_inverted_index.tools	25
abstract_inverted_index.virus	49
abstract_inverted_index.which	63
abstract_inverted_index.(CCM).	20
abstract_inverted_index.(rAAV)	50
abstract_inverted_index.MAP3K3	130
abstract_inverted_index.cells,	61
abstract_inverted_index.global	180
abstract_inverted_index.severe	9
abstract_inverted_index.stages	109, 117
abstract_inverted_index.system	82, 165
abstract_inverted_index.widely	170
abstract_inverted_index.-system	55
abstract_inverted_index.Defects	1
abstract_inverted_index.achieve	95
abstract_inverted_index.brainEC	155, 181
abstract_inverted_index.develop	45
abstract_inverted_index.disease	28, 175
abstract_inverted_index.element	72
abstract_inverted_index.genetic	32
abstract_inverted_index.hinders	38
abstract_inverted_index.induces	149
abstract_inverted_index.minimal	66
abstract_inverted_index.somatic	142
abstract_inverted_index.through	103, 111
abstract_inverted_index.various	107
abstract_inverted_index.Abstract	0
abstract_inverted_index.achieves	83
abstract_inverted_index.brainECs	102, 148
abstract_inverted_index.cerebral	17
abstract_inverted_index.combines	64
abstract_inverted_index.isolated	74
abstract_inverted_index.mediated	128, 134
abstract_inverted_index.miniBEND	52
abstract_inverted_index.modeling	29, 176
abstract_inverted_index.othelial	60
abstract_inverted_index.promoter	67
abstract_inverted_index.provides	166
abstract_inverted_index.research	39
abstract_inverted_index.sporadic	126
abstract_inverted_index.valuable	168
abstract_inverted_index.brainECs.	91
abstract_inverted_index.cavernous	18
abstract_inverted_index.delivery.	183
abstract_inverted_index.important	158
abstract_inverted_index.including	12
abstract_inverted_index.injection	105
abstract_inverted_index.optimized	70
abstract_inverted_index.postnatal	116
abstract_inverted_index.(brainECs)	6
abstract_inverted_index.applicable	171
abstract_inverted_index.cis-acting	71
abstract_inverted_index.expression	85, 100, 143
abstract_inverted_index.phenotype,	152
abstract_inverted_index.(rAAV-based	53
abstract_inverted_index.appropriate	24
abstract_inverted_index.demonstrate	140
abstract_inverted_index.endothelial	4
abstract_inverted_index.intravenous	112
abstract_inverted_index.recombinant	47
abstract_inverted_index.vasculature	37
abstract_inverted_index.Furthermore,	120
abstract_inverted_index.development.	161
abstract_inverted_index.intracranial	104
abstract_inverted_index.malformation	14, 19
abstract_inverted_index.manipulation	33
abstract_inverted_index.specifically	86
abstract_inverted_index.(cis-element)	73
abstract_inverted_index.arteriovenous	13
abstract_inverted_index.developmental	108
abstract_inverted_index.proliferation	156
abstract_inverted_index.rAAV-miniBEND	123, 164
abstract_inverted_index.administration	113
abstract_inverted_index.malformations,	11
abstract_inverted_index.malformations.	42
abstract_inverted_index.rAAV-miniBEND,	93
abstract_inverted_index.cerebrovascular	10, 27, 41, 174
abstract_inverted_index.high-efficiency	96
abstract_inverted_index.rAAV-miniBEND),	62
abstract_inverted_index.adeno-associated	48
abstract_inverted_index.high-specificity	98
cited_by_percentile_year.max	95
cited_by_percentile_year.min	91
countries_distinct_count	0
institutions_distinct_count	19
citation_normalized_percentile.value	0.84070751
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	True