脑回路障碍的按需细胞自主基因治疗。开发了一种基因治疗策略，可以自我选择病理上过度活跃的神经元，并在闭环中下调它们的兴奋性。钾离子通道。本论文是用基因疗法、让异常的神经元细胞兴奋性恢复正常，应用于治疗神经系统难病癫痫，并在将来进一步扩展治疗其他神经精神系统疾病如帕金森氏病、精神分裂症等的基础医学研究论文。
(Baidu Translation： )
Science: Epilepsy frequency decreased by 80%! Innovative gene therapy shows amazing results, and it's too bad
On-demand cellular autonomous gene therapy for brain circuit disorders. A gene therapy strategy has been developed that can self-select pathologically hyperactive neurons and down-regulate their excitability in a closed loop. Potassium ion channel. This paper is a basic medical research paper that uses gene therapy to restore the excitability of abnormal neurons to normal, which is used to treat the intractable epilepsy of the nervous system, and further expand the treatment of other neuropsychiatric diseases such as Parkinson's disease and schizophrenia in the future.
（百度翻訳： ）
『科学』：てんかん発作頻度が80%低下！革新的遺伝子療法は驚くべき成果を示し、過興を下げる
脳回路障害のオンデマンド細胞自主遺伝子治療。病理的に過度に活発なニューロンを自己選択し、閉ループ中に興奮性を低下させる遺伝子治療戦略を開発した。カリウムイオンチャンネル。本論文は遺伝子療法を用いて、異常なニューロン細胞の興奮性を正常に回復させ、神経系難病てんかんの治療に応用し、将来的にパーキンソン病、統合失調症などの他の神経精神系疾患の治療をさらに拡張する基礎医学研究論文である。
药明康德
2022/11/23
论文
论文标题：On-demand cell-autonomous gene therapy for brain circuit disorders
作者：Yichen Qiu, Nathanael O’Neill, Benito Maffei, Clara Zourray, Amanda Almacellas-Barbanoj, Jenna C. Carpenter, Steffan P. Jones, Marco Leite, Thomas J. Turner, Francisco C. Moreira, Albert Snowball, Tawfeeq Shekh-Ahmad, Vincent Magloire, Serena Barral, Manju A. Kurian, Matthew C. Walker, Stephanie Schorge, Dimitri M. Kullmann, Gabriele Lignani
期刊：Science
发表时间：2022/11/04
数字识别码：10.1126/science.abq6656
摘要：Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and “healthy” surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.
