An ultra-compact promoter drives widespread neuronal expression in mouse and monkey brains

作者：Wang, Jingyi; Lin, Jianbang; Chen, Yefei; Liu, Jing; Zheng, Qiongping; Deng, Mao; Wang, Ruiqi; Zhang, Yujing; Feng, Shijing; Xu, Zhenyan; Ye, Weiyi; Hu, Yu; Duan, Jiamei; Lin, Yunping; Dai, Ji; Chen, Yu; Li, Yuantao; Luo, Tao; Chen, Qian^*; Lu, Zhonghua^*

来源：Cell Reports, 2023, 42(11): 113348.

DOI：10.1016/j.celrep.2023.113348

• AUTISTIC-LIKE BEHAVIORS
• ADENOASSOCIATED VIRUS
• TRANSGENE EXPRESSION
• GENE DELIVERY
• VECTOR
• RECOMBINATION
• OPPORTUNITIES
• INTERNEURONS
• CHALLENGES
• VARIANTS

Promoters are essential tools for basic and translational neuroscience research. An ideal promoter should possess the shortest possible DNA sequence with cell-type selectivity. However, whether ultra-compact pro-moters can offer neuron-specific expression is unclear. Here, we report the development of an extremely short promoter that enables selective gene expression in neurons, but not glial cells, in the brain. The pro-moter sequence originates from the human CALM1 gene and is only 120 bp in size. The CALM1 promoter (pCALM1) embedded in an adeno-associated virus (AAV) genome directed broad reporter expression in excitatory and inhibitory neurons in mouse and monkey brains. Moreover, pCALM1, when inserted into an all-in-one AAV vector expressing SpCas9 and sgRNA, drives constitutive and conditional in vivo gene editing in neurons and elicits functional alterations. These data demonstrate the ability of pCALM1 to conduct restricted neuronal gene expression, illustrating the feasibility of ultra-miniature promoters for targeting brain-cell subtypes.

• 单位
  中国科学院研究生院; 北京大学; 南方医科大学