Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons

Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. Th...

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Main Authors: Benjamin D. W. Belfort, Johnathan D. Jia, Alexandra R. Garza, Anthony M. Insalaco, J. P. McGinnis, Brandon T. Pekarek, Joshua Ortiz-Guzman, Burak Tepe, Hu Chen, aSCENT-PD Investigators, Zhandong Liu, Benjamin R. Arenkiel, Benjamin Arenkiel, Brit Mollenhauer, Josef Penninger, Maxime Rousseaux, Armen Saghatelyan, Natalina Salmaso, Christine Stadelmann, Michael G. Schlossmacher, Julianna J. Tomlinson, John M. Woulfe, Ying Wang, Zihong Chen, Mira Jeong
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1531122/full
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author Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Johnathan D. Jia
Johnathan D. Jia
Johnathan D. Jia
Alexandra R. Garza
Alexandra R. Garza
Alexandra R. Garza
Alexandra R. Garza
Anthony M. Insalaco
Anthony M. Insalaco
J. P. McGinnis
J. P. McGinnis
Brandon T. Pekarek
Brandon T. Pekarek
Brandon T. Pekarek
Joshua Ortiz-Guzman
Burak Tepe
Burak Tepe
Hu Chen
Hu Chen
Hu Chen
aSCENT-PD Investigators
Zhandong Liu
Zhandong Liu
Zhandong Liu
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin Arenkiel
Zhandong Liu
Brit Mollenhauer
Josef Penninger
Maxime Rousseaux
Armen Saghatelyan
Natalina Salmaso
Christine Stadelmann
Michael G. Schlossmacher
Julianna J. Tomlinson
John M. Woulfe
Ying Wang
Zihong Chen
Mira Jeong
author_facet Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Johnathan D. Jia
Johnathan D. Jia
Johnathan D. Jia
Alexandra R. Garza
Alexandra R. Garza
Alexandra R. Garza
Alexandra R. Garza
Anthony M. Insalaco
Anthony M. Insalaco
J. P. McGinnis
J. P. McGinnis
Brandon T. Pekarek
Brandon T. Pekarek
Brandon T. Pekarek
Joshua Ortiz-Guzman
Burak Tepe
Burak Tepe
Hu Chen
Hu Chen
Hu Chen
aSCENT-PD Investigators
Zhandong Liu
Zhandong Liu
Zhandong Liu
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin Arenkiel
Zhandong Liu
Brit Mollenhauer
Josef Penninger
Maxime Rousseaux
Armen Saghatelyan
Natalina Salmaso
Christine Stadelmann
Michael G. Schlossmacher
Julianna J. Tomlinson
John M. Woulfe
Ying Wang
Zihong Chen
Mira Jeong
author_sort Benjamin D. W. Belfort
collection DOAJ
description Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons in vivo. Here we utilized serial confocal imaging and single-nucleus RNA sequencing to evaluate the efficacy of 11 different AAV serotypes in transducing murine olfactory sensory neurons via non-invasive nasal inoculation. Our results reveal that AAV1, while highly effective, exhibited broad tropism, whereas AAV-DJ/8 showed the greatest specificity for olfactory sensory neurons.
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spelling doaj-art-d7b642777bcc4587b81b8a3d8e3a95eb2025-08-20T03:11:33ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-02-011910.3389/fnins.2025.15311221531122Comparative analysis of AAV serotypes for transduction of olfactory sensory neuronsBenjamin D. W. Belfort0Benjamin D. W. Belfort1Benjamin D. W. Belfort2Benjamin D. W. Belfort3Benjamin D. W. Belfort4Johnathan D. Jia5Johnathan D. Jia6Johnathan D. Jia7Alexandra R. Garza8Alexandra R. Garza9Alexandra R. Garza10Alexandra R. Garza11Anthony M. Insalaco12Anthony M. Insalaco13J. P. McGinnis14J. P. McGinnis15Brandon T. Pekarek16Brandon T. Pekarek17Brandon T. Pekarek18Joshua Ortiz-Guzman19Burak Tepe20Burak Tepe21Hu Chen22Hu Chen23Hu Chen24aSCENT-PD Investigators25Zhandong Liu26Zhandong Liu27Zhandong Liu28Benjamin R. Arenkiel29Benjamin R. Arenkiel30Benjamin R. Arenkiel31Benjamin R. Arenkiel32Benjamin ArenkielZhandong LiuBrit MollenhauerJosef PenningerMaxime RousseauxArmen SaghatelyanNatalina SalmasoChristine StadelmannMichael G. SchlossmacherJulianna J. TomlinsonJohn M. WoulfeYing WangZihong ChenMira JeongGenetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesMedical Scientist Training Program, Baylor College of Medicine, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesSection of Neurology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United StatesGenetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, United StatesGenetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesSection of Neurology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesSection of Neurology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United StatesAligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesOlfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons in vivo. Here we utilized serial confocal imaging and single-nucleus RNA sequencing to evaluate the efficacy of 11 different AAV serotypes in transducing murine olfactory sensory neurons via non-invasive nasal inoculation. Our results reveal that AAV1, while highly effective, exhibited broad tropism, whereas AAV-DJ/8 showed the greatest specificity for olfactory sensory neurons.https://www.frontiersin.org/articles/10.3389/fnins.2025.1531122/fullAAVsnRNAseqgene therapyolfactionolfactory sensory neurons
spellingShingle Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Benjamin D. W. Belfort
Johnathan D. Jia
Johnathan D. Jia
Johnathan D. Jia
Alexandra R. Garza
Alexandra R. Garza
Alexandra R. Garza
Alexandra R. Garza
Anthony M. Insalaco
Anthony M. Insalaco
J. P. McGinnis
J. P. McGinnis
Brandon T. Pekarek
Brandon T. Pekarek
Brandon T. Pekarek
Joshua Ortiz-Guzman
Burak Tepe
Burak Tepe
Hu Chen
Hu Chen
Hu Chen
aSCENT-PD Investigators
Zhandong Liu
Zhandong Liu
Zhandong Liu
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin R. Arenkiel
Benjamin Arenkiel
Zhandong Liu
Brit Mollenhauer
Josef Penninger
Maxime Rousseaux
Armen Saghatelyan
Natalina Salmaso
Christine Stadelmann
Michael G. Schlossmacher
Julianna J. Tomlinson
John M. Woulfe
Ying Wang
Zihong Chen
Mira Jeong
Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
Frontiers in Neuroscience
AAV
snRNAseq
gene therapy
olfaction
olfactory sensory neurons
title Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
title_full Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
title_fullStr Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
title_full_unstemmed Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
title_short Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
title_sort comparative analysis of aav serotypes for transduction of olfactory sensory neurons
topic AAV
snRNAseq
gene therapy
olfaction
olfactory sensory neurons
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1531122/full
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