相关实验视频

Updated: May 30, 2025

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models

Published on: March 29, 2019

在iPSC衍生神经元中通过个性化基层编辑来建模和纠正蛋白质构造性疾病

Colin T Konishi^1,2, Nancy Mulaiese^1,2, Tanvi Butola³

¹NYU Cardiovascular Research Center, NYU Grossman School of Medicine, New York, NY 100016, USA.

Molecular therapy. Nucleic acids

|January 29, 2025

概括

基因编辑提供了一种有前途的方法来纠正导致神经胺纳入体 (FENIB) 的家族脑病变的神经胺突变. 这项研究证明了有效的校正,减少有毒蛋白质聚合物并恢复神经元健康.

科学领域:

神经科学是一个神经科学.
遗传学遗传学是一个
分子生物学分子生物学

背景情况:

变化的蛋白质构造与不可治愈的神经退行性疾病有关.
神经蛋白基因 (SERPINI1) 的突变导致细胞毒性聚合和神经元死亡,导致FENIB,一种罕见的渐进性.
费尼布的特点是痴呆和过早死亡.

研究的目的:

开发和验证FENIB的腺基编辑器 (ABE) 介导的基因校正.
在FENIB模型中恢复神经元形态并减少有毒蛋白质聚合物.
优化ABE输送,以在神经退行性疾病中潜在的临床应用.

主要方法:

已建立的HEK293T和诱导多能干细胞 (iPSC) 模型的FENIB.
使用个性化的ABE介导方法来纠正致病性SERPINI1变种.
开发了一种神经元特异性工程病毒样粒子,用于增强ABE传递.

主要成果:

ABE治疗有效地纠正了致病性SERPINI1变体,恢复了神经元树突形态.
MUT NS-GFP细胞显示了减少的大小和神经胺含的数量.
早期预防有毒蛋白质表达导致聚合物清除,而晚期预防则阻止聚合.

结论:

由ABE介导的基因校正是FENIB的一种有针对性的策略.
优化病毒载体传递可以提高神经元中的ABE效率.
这种方法有可能用于治疗FENIB和其他蛋白质错折的神经退行性疾病,如阿尔茨海默氏症和亨廷顿氏症.

关键词:

克里斯普尔-Cas9是什么意思 MT:RNA/DNA编辑编辑基编辑基编辑人工设计的类似病毒的粒子.由iPSC衍生的神经元.蛋白质聚合蛋白质的聚合物蛋白质构造性疾病是一种蛋白质构造性疾病.

更多相关视频

Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development

Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development

Published on: March 5, 2017

Efficient Generation and Editing of Feeder-free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System

Efficient Generation and Editing of Feeder-free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System

Published on: November 8, 2017

相关概念视频

EPS and iPS Cells in Disease Research

EPS and iPS Cells in Disease Research

Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...

iPS Cell Differentiation

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.