Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein

Abstract Rabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic ne...

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Main Authors: Fan Jia, Li Li, Haizhou Liu, Pei Lv, Xiangwei Shi, Yang Wu, Chen Ling, Fuqiang Xu
Format: Article
Language:English
Published: BMC 2021-07-01
Series:Molecular Brain
Online Access:https://doi.org/10.1186/s13041-021-00821-7
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author Fan Jia
Li Li
Haizhou Liu
Pei Lv
Xiangwei Shi
Yang Wu
Chen Ling
Fuqiang Xu
author_facet Fan Jia
Li Li
Haizhou Liu
Pei Lv
Xiangwei Shi
Yang Wu
Chen Ling
Fuqiang Xu
author_sort Fan Jia
collection DOAJ
description Abstract Rabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.
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spelling doaj.art-c89189569de84ba892a825e876251be72022-12-21T22:01:11ZengBMCMolecular Brain1756-66062021-07-011411910.1186/s13041-021-00821-7Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoproteinFan Jia0Li Li1Haizhou Liu2Pei Lv3Xiangwei Shi4Yang Wu5Chen Ling6Fuqiang Xu7Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute (BCBDI), Translational Research Center for the Nervous System (TRCNS), Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems,, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of SciencesWuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems,, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of SciencesState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems,, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of SciencesState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems,, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of SciencesDivision of Molecular and Cellular Therapy, Department of Pediatrics, College of Medicine, University of FloridaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute (BCBDI), Translational Research Center for the Nervous System (TRCNS), Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesAbstract Rabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.https://doi.org/10.1186/s13041-021-00821-7
spellingShingle Fan Jia
Li Li
Haizhou Liu
Pei Lv
Xiangwei Shi
Yang Wu
Chen Ling
Fuqiang Xu
Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
Molecular Brain
title Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
title_full Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
title_fullStr Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
title_full_unstemmed Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
title_short Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
title_sort development of a rabies virus based retrograde tracer with high trans monosynaptic efficiency by reshuffling glycoprotein
url https://doi.org/10.1186/s13041-021-00821-7
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