StitchR-based dual-AAV delivery strategies enable efficient transduction of defined neural cell populations.
9 affiliations
- 1Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
- 2Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
- 3Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, People's Republic of China.
- 4Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441106, People's Republic of China.
- 5Brain Case Biotechnology Co., Ltd., Shenzhen, 518107, People's Republic of China.
- 6Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China. [email protected].
- 7Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China. [email protected].
- 8Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, People's Republic of China. [email protected].
- 9Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China. [email protected].
Abstract
Dual adeno-associated virus (AAV) vector reconstitution has become an indispensable technique for delivering large genes in neuroscience and gene therapy. A novel technology termed StitchR addresses the challenge of low efficiency in dual-AAV reconstruction, yet related tools enabling targeted gene delivery to specific neural cell populations remain insufficiently developed. Herein, we developed four StitchR-based dual-viral reconstitution strategies by combining high-efficiency AAV serotypes with neuron- or glia-specific promoters. Specifically, the AAV11-hSyn-driven StitchR strategy achieved specific transduction of local neurons and their upstream projection neurons (≥ 94.44% specificity); the AAV11-GfaABC1D-driven strategy realized astrocyte-specific transduction (approximately 98.25% specificity); and the AAV11-mIBA1-driven strategy enabled microglia-specific transduction (100% specificity). Furthermore, by incorporating the blood-brain barrier (BBB)-penetrating AAVhu.32-PLUS into the hSyn-driven system, we established a modified strategy that allows brain-wide neuronal transduction. Finally, we confirmed that the StitchR-based dual-viral reconstitution strategy can achieve efficient functional reconstitution of large transgenes in neural cells. Collectively, these dual-AAV delivery strategies expand the valuable AAV toolbox and offer crucial technical support for targeted delivery of large transgenes to defined neural cell populations, holding great significance for basic neuroscience research and potential therapeutic applications.
Related
- AAV-DJ enables efficient, function-preserving neuronal transduction for circuit interrogation in human cortical and thalamic organoids
- Wild Luteibacter populations exhibit climate-associated divergence and distinct genomic strategies for osmotic stress tolerance
- Cellulose Nanocrystal/Zn‐MOF Nanocarriers for Enhanced Foliar Adhesion, pH‐Responsive Release, and Efficient Pesticide Delivery
- Enhancing food digestion and nutrient absorption through pre-digestion: Tailored strategies for special populations
- Conservation Management Strategies Shape Glucocorticoid Levels in African Elephant Populations More Than Parasite Load
BibTeX
@article{luo2026stitchrbased,
title = {{StitchR-based dual-AAV delivery strategies enable efficient transduction of defined neural cell populations.}},
author = {Nengsong Luo and Yunling Gao and Zengpeng Han and Peng Su and Fuqiang Xu and Kunzhang Lin},
journal = {Molecular brain},
year = {2026},
month = jul,
doi = {10.1186/s13041-026-01331-0},
url = {https://europepmc.org/article/MED/42902394},
note = {CC BY},
}
RIS
TY - JOUR
TI - StitchR-based dual-AAV delivery strategies enable efficient transduction of defined neural cell populations.
AU - Nengsong Luo
AU - Yunling Gao
AU - Zengpeng Han
AU - Peng Su
AU - Fuqiang Xu
AU - Kunzhang Lin
PY - 2026
DA - 2026/07/01
JO - Molecular brain
DO - 10.1186/s13041-026-01331-0
UR - https://europepmc.org/article/MED/42902394
AB - Dual adeno-associated virus (AAV) vector reconstitution has become an indispensable technique for delivering large genes in neuroscience and gene therapy. A novel technology termed StitchR addresses the challenge of low efficiency in dual-AAV reconstruction, yet related tools enabling targeted gene delivery to specific neural cell populations remain insufficiently developed. Herein, we developed four StitchR-based dual-viral reconstitution strategies by combining high-efficiency AAV serotypes with neuron- or glia-specific promoters. Specifically, the AAV11-hSyn-driven StitchR strategy achieved specific transduction of local neurons and their upstream projection neurons (≥ 94.44% specificity); the AAV11-GfaABC1D-driven strategy realized astrocyte-specific transduction (approximately 98.25% specificity); and the AAV11-mIBA1-driven strategy enabled microglia-specific transduction (100% specificity). Furthermore, by incorporating the blood-brain barrier (BBB)-penetrating AAVhu.32-PLUS into the hSyn-driven system, we established a modified strategy that allows brain-wide neuronal transduction. Finally, we confirmed that the StitchR-based dual-viral reconstitution strategy can achieve efficient functional reconstitution of large transgenes in neural cells. Collectively, these dual-AAV delivery strategies expand the valuable AAV toolbox and offer crucial technical support for targeted delivery of large transgenes to defined neural cell populations, holding great significance for basic neuroscience research and potential therapeutic applications.
SN - 1756-6606
ER -