Engineered AAV13 variants with enhanced transduction and confined spread

作     者：Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu Neng-Song Luo;Yu-Xiang Cai;Zeng-Peng Han;Xiao-Kai Sui;Wen-Jia Yuan;Zi-Lian Zhang;Hao-Dong Guo;Jie Wang;Kun-Zhang Lin;Fu-Qiang Xu

作者机构：Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in Biological SystemsState Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of SciencesBeijing 100049China Zhongnan HospitalWuhan UniversityWuhanHubei 430072China Brain Case Biotechnology Co.Ltd.ShenzhenGuangdong 518107China College of Life SciencesWuhan UniversityWuhanHubei 430072China Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2024年第45卷第4期

页      面：781-790页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 08[工学] 1010[医学-医学技术（可授医学、理学学位）] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 100215[医学-康复医学与理疗学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 10[医学] 

基　　金：National Science and Technology Innovation 2030 Grant(2021ZD0201003) National Natural Science Foundation of China(31830035,31771156,21921004) Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030200) Shenzhen Key Laboratory of Viral Vectors for Biomedicine(ZDSYS20200811142401005) Key Laboratory of Quality Control Technology for Virus-Based Therapeutics,Guangdong Provincial Medical Products Administration(2022ZDZ13) 

主　　题：Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency 

摘      要：Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the context of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.