Advanced Science. 2023 Sep 8
Caijuan Li, Yingqi Lin, Yizhi Chen, Xichen Song, Xiao Zheng, Jiawei Li, Jun He, Xiusheng Chen, Chunhui Huang, Wei Wang, Jianhao Wu, Jiaxi Wu, Jiale Gao, Zhuchi Tu, Xiao-Jiang Li, Sen Yan, Shihua Li
Products used in the paper Details Operation
AAV vector packaging For AAV used in brain stereotaxic and intravenous injections, AAV-PHP. eB: SM3 and control virus AAV-PHP. eB: GFP were packaged and purified by PackGene Biotech (PackGene, Guangzhou, China). Request Quote

Research Field: CNS

Keywords: HD KI-140Q mice, intravenous injection, lysosome, mini-intrabody, mutant huntingtin, SM3, stereotaxic injection

AAV Serotype: AAV.PHP.eB

Dose: 1E10/mouse

Routes of Administration: brain stereotaxic injection

Targeted organ: brain

Animal or cell line strain: Mouse


Accumulation of misfolded proteins leads to many neurodegenerative diseases that can be treated by lowering or removing mutant proteins. Huntington’s disease (HD) is characterized by the intracellular accumulation of mutant huntingtin (mHTT) that can be soluble and aggregated in the central nervous system and causes neuronal damage and death. Here, an intracellular antibody (intrabody) fragment is generated that can specifically bind mHTT and link to the lysosome for degradation. It is found that delivery of this peptide by either brain injection or intravenous administration can efficiently clear the soluble and aggregated mHTT by activating the lysosomal degradation pathway, resulting in amelioration of gliosis and dyskinesia in HD knock-in (KI-140Q) mice. These findings suggest that the small intrabody peptide linked to lysosomes can effectively lower mutant proteins and provide a new approach for treating neurodegenerative diseases that are caused by the accumulation of mutant proteins.

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