Mind endothelial cells (BEC) focused by a BEC-enhancer AAV vector software, developed by the Xu Lab and the Middle for Neural Circuit Mapping workforce. Viral labeling (inexperienced) overlaps with endothelial cells (magenta) and protein markers for mind blood vessels (blue). Credit score: Xu Lab
New research stemming from the Armamentarium consortium define findings that advance instruments based mostly on Adeno-associated virus (AAV) vectors. An announcement concerning the work explains how an AAV “acts like a shuttle capable of transporting specially designed DNA into the cell.”
Two of the research on these AAV instruments have been performed by collaborative groups organized by Xiangmin Xu, Ph.D., UC Irvine Chancellor’s Professor of anatomy and neurobiology and director of the campus’s Middle for Neural Circuit Mapping.
“This Armamentarium’s collection of work enables new tools that help to deepen our understanding of the human central nervous system structure and function,” says Xu. “Our own brain-targeting technology could help treat Alzheimer’s disease and many other neurological disorders.”
Concentrating on mind endothelial cells
One of many two papers, “Specific targeting of brain endothelial cells using enhancer-AAV vectors,” by Eric Velazquez-Rivera, Oyshi Dey, Nayoon Sophie Kim, Wenhao Cao, Qiao Ye, Hai Zhang, Jonathan T. Ting, Bing Ren, Todd C. Holmes, and Xiangmin Xu, seems on-line within the Might 21, 2025 launch of Neuron.
This collaboration between researchers at UC Irvine, UC San Diego and the Allen Institute for Mind Science targets sure blood vessels within the mind.
“Blood flow through the brain goes through a special set of blood vessels that provides special protection to the brain,” explains Velazquez-Rivera, a postdoctoral researcher within the Xu Lab. This particular vasculature is a key part of the blood mind barrier (BBB). “Drug delivery to the brain is a big challenge due to this barrier, but we have developed a way to circumvent the BBB with a technology that targets brain vasculature with minimal unwanted side effects.”
Leveraging the variations in these blood vessels in comparison with the remainder of the physique, the researchers developed a brand new expertise, based mostly on genomic enhancer sequences and recombinant AAV vectors, that targets the mind’s endothelial cells (BEC) with excessive specificity.
“We tested our BEC-targeting technology in an Alzheimer’s disease mouse model with very aggressive pathology and, remarkably, it was still specific and effective,” says Velazquez-Rivera. “The capability to target with high specificity the endothelial cells in the brain can open the door to the development of new gene therapy vectors for a broad array of neurological diseases.”
The researchers hope to finally use the BEC-enhancer AAV to ship therapeutic medicine to the mind. “Our BEC AAV vector tools could be used for brain-targeted gene therapy to ameliorate neurological diseases,” says Velazquez-Rivera. “It may even be used someday to treat stroke victims.”
One of many senior authors, Todd Holmes, Ph.D., professor of physiology and biophysics at UC Irvine, remembers the origins of the work. “Just over five years ago, Dr. Xu and I and UCI School of Medicine colleagues developed a bold vision that we could work towards curing then-untreatable diseases by creating new technologies and by partnering with some of the best minds in the fields of neuroscience, genomics, virology, biomedical engineering, computer science and mathematics,” he says. “This paper, and other recent papers from our scientific dream team, are products of that vision.”
Concentrating on forebrain excitatory neurons
The opposite paper, “An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons,” by Wenhao Cao, Zhiqun Tan, Bereket T. Berackey, Jason Okay. Nguyen, Sara R. Brown, Shiyang Du, Bin Lin, Qiao Ye, Magdalene Seiler, Todd C. Holmes and Xiangmin Xu, seems on-line within the Might 21, 2025 launch of Cell Reviews Strategies.
This work targets excitatory neurons, cells which can be actively concerned in cognitive reminiscence and spatial navigation. Particularly, it examines AAV-MG1.2, a software that allows focused gene supply to excitatory neurons within the mind.
Labeling of CA1 excitatory neurons utilizing the AAV-MG1.2 capsid. Excitatory neurons seem in inexperienced, cell nuclei are stained with DAPI (blue), inhibitory neurons are marked in cyan, and astrocytes are proven in crimson. Credit score: Xu Lab
“Our group found that AAV-MG1.2 actually achieves specific genetic expression in an entirely different brain cell type: excitatory neurons in the forebrain region across different animal species,” says Cao, a graduate scholar researcher within the Xu Lab. He stresses that this discovering disproves earlier claims. Moreover, the researchers have been capable of validate functions for this AAV software within the neural circuit tracing and reveal enter connections for excitatory neurons in each hippocampal and cortical areas—areas which can be vital for cognition, studying and reminiscence.
“Our study expands the existing toolbox for targeting excitatory neurons and presents AAV-MG1.2 as a useful tool for targeting functional payloads to subsets of excitatory neurons in the forebrain across different species,” says Cao. “When coupled with functional enhancer elements designated for distinct excitatory neuronal subtypes, AAV-MG1.2 opens up a promising avenue for exploring specific brain cell subtypes, which could eventually lead to clinical applications that facilitate targeted therapy.”
The researchers will proceed to discover the inside workings of AAV-MG1.2. “The biological mechanism underlying AAV-MG1.2’s specific targeting of excitatory neurons remains unclear,” says Cao. “Elucidating this mechanism will be critical for expanding the toolbox of AAV-based tools used in neuroscience research.”
Extra data:
Eric Velazquez-Rivera et al, Particular focusing on of mind endothelial cells utilizing enhancer AAV vectors, Neuron (2025). DOI: 10.1016/j.neuron.2025.03.031
Wenhao Cao et al, An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons, Cell Reviews Strategies (2025). DOI: 10.1016/j.crmeth.2025.101054
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