利用增强的原始编辑来阻止异常血管生成
Xionggao Huang1, Wenyi Wu2, Hui Qi3
1Department of Ophthalmology, The First Affiliated Hospital of Hainan Medical University, Haikou, China.
Journal of advanced research
|July 12, 2024
概括
主编辑成功地产生了主导负的VEGFR2,以阻止小鼠的病态视网膜血管生成. 这种基因编辑方法为挑战血管疾病提供了新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 基因编辑 基因编辑
- 眼科医生 眼科 眼科
背景情况:
- 异常血管生成有助于诸如增殖性糖尿病视网膜病变等疾病.
- 主编辑 (PE) 为具有挑战性的疾病提供了一种新的基因编辑方法.
研究的目的:
- 使用主要编辑创建主导负 (DN) 血管内皮生长因子受体 (VEGFR) 2.
- 在氧气诱导视网膜病变的小鼠模型中阻止异常视网膜血管生成.
主要方法:
- 一个先进的prime编辑系统 (PE6x) 使用双lentiviral向量被开发出来.
- 使用非整合性隐形病毒 (NILVs) 来编辑肌肉肌 VEGFR2 位点,创建一个过早的停止编码子来产生 DN-VEGFR2.
- 该系统在实验室中对小鼠血管内皮细胞进行了测试,并在氧气诱导视网膜病变的小鼠模型中进行了体内测试.
主要成果:
- PE6x系统在体外实现了51.06%的VEGFR2 T17967A编辑,产生了阻碍VEGF诱导酸化的DN-VEGFR2.
- 在小鼠体内注射NILV导致视网膜DN-VEGFR2的产生,阻断VEGFR2的激活和异常的视网膜血管生成.
- 视网膜结构和功能没有受到影响,各种评估证实了这一点.
结论:
- 使用PE6x主要编辑系统编辑基因组VEGFR2,生成DN-VEGFR2.
- 这种DN-VEGFR2可用于治疗眼内病理性血管生成.
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