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 

机构地区：[1]Wuhan National Laboratory for Optoelectronics,Huazhong University of Science and Technology,Wuhan,Hubei 430074,China [2]Shenzhen Key Laboratory of Viral Vectors for Biomedicine,Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong 518055,China [3]Key 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,Hubei 430071,China [4]Key Laboratory of Quality Control Technology for Virus-Based Therapeutics,Guangdong Provincial Medical Products Administration,NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products,Brain Cognition and Brain Disease Institute,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong 518055,China [5]University of Chinese Academy of Sciences,Beijing 100049,China [6]Zhongnan Hospital,Wuhan University,Wuhan,Hubei 430072,China [7]Brain Case Biotechnology Co.,Ltd.,Shenzhen,Guangdong 518107,China [8]College of Life Sciences,Wuhan University,Wuhan,Hubei 430072,China [9]Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Shanghai 200031,China

出　　处：《Zoological Research》2024年第4期781-790,共10页动物学研究（英文）

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)。

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 diseases.Adeno-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 regions.However,AAV13 mediates relatively low expression of target genes.Here,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency.We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid.We 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,respectively.We 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 range.These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关 键 词：Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency 

分 类 号：R450[医药卫生—治疗学] Q78[医药卫生—临床医学]