Enhancing Transgene Expression and Retention by Co-delivery of DNA Vectors with Modified Histones

通过 DNA 载体与修饰组蛋白的共同传递增强转基因表达和保留

• 批准号: 1705560
• 负责人: Chongli Yuan
• 金额: $ 45万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1705560&HistoricalAwards=false
• 关键词: Enhancing; Transgene; Expression; Retention; Co

Gene therapy has been offered as a potential cure for a wide range of diseases, including hemophilia, cystic fibrosis, Parkinson's, HIV, hepatitis, and heart disease. Conventional gene delivery approaches currently lack the safety, efficiency and durability required for many research, industrial and/or clinical applications. Understanding how to create and maintain active gene expression will have broad-ranging impacts on gene delivery and expression in humans. The proposed work will bring effective gene therapies closer to reality, and will also train and inspire the next generation of scientists and engineers through their active participation in this interdisciplinary research.The long-term objective of this project is to elucidate how long-term cellular memories of transcriptional states are created and maintained to advance research, industrial and gene therapy applications requiring regulated transgene expression. The specific scientific objectives are to 1) develop a robust strategy for co-delivering transgenes together with modified histone proteins promoting active transcription; and 2) evaluate and enhance protein expression from chromatin assembled on transgenic DNA. The established delivery approach is expected to significantly improve the uptake and controlled expression of transgenic DNA and to be compatible with a broad range of vectors. The fundamental kowledge gained regarding the design of epigenetic systems for heterologous gene expression could have profound implications for all eukaryotic gene expression systems. Such insight could, for example, significantly expand the scope and efficacy of human gene therapy, leading to cures for many serious diseases.

基因疗法已成为治疗多种疾病的潜在疗法，包括血友病、囊性纤维化、帕金森病、艾滋病毒、肝炎和心脏病。传统的基因递送方法目前缺乏许多研究、工业和/或临床应用所需的安全性、效率和耐久性。了解如何创建和维持活跃的基因表达将对人类基因传递和表达产生广泛的影响。拟议的工作将使有效的基因疗法更接近现实，并将通过积极参与这项跨学科研究来培训和激励下一代科学家和工程师。该项目的长期目标是阐明如何创建和维持转录状态的长期细胞记忆，以推进需要调控转基因表达的研究、工业和基因治疗应用。具体的科学目标是 1) 开发一种强有力的策略，将转基因与促进活性转录的修饰组蛋白一起共同传递； 2) 评估并增强转基因 DNA 上组装的染色质的蛋白质表达。所建立的递送方法预计将显着改善转基因 DNA 的摄取和受控表达，并与广泛的载体兼容。关于异源基因表达的表观遗传系统设计所获得的基本知识可能对所有真核基因表达系统产生深远的影响。例如，这种洞察力可以显着扩大人类基因治疗的范围和功效，从而治愈许多严重的疾病。

项目成果

Pre-differentiation exposure to low-dose of atrazine results in persistent phenotypic changes in human neuronal cell lines

分化前暴露于低剂量莠去津会导致人类神经细胞系持续表型变化

• DOI: 10.1016/j.envpol.2020.116379
• 发表时间: 2021
• 期刊: Environmental Pollution
• 影响因子: 8.9
• 作者: Xie, Junkai;Lin, Li;Sánchez, Oscar F.;Bryan, Chris;Freeman, Jennifer L.;Yuan, Chongli
• 通讯作者: Yuan, Chongli

Review: Engineering in situ biosensors for tracking cellular events

• DOI: 10.1016/j.coche.2020.06.006
• 发表时间: 2020-12
• 期刊: Current opinion in chemical engineering
• 影响因子: 6.6
• 作者: Kyle Wettschurack;Junkai Xie;Oscar F. Sánchez;Chongli Yuan

Identifying distinct heterochromatin regions using combinatorial epigenetic probes in live cells

• DOI: 10.1016/j.bbagrm.2021.194725
• 发表时间: 2021-06-26
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
• 影响因子: 4.7
• 作者: Mendonca，Agnes;Sanchez，Oscar F.;Yuan，Chongli
• 通讯作者: Yuan，Chongli

Monitoring Histone Methylation (H3K9me3) Changes in Live Cells

监测活细胞中组蛋白甲基化 (H3K9me3) 的变化

• DOI: 10.1021/acsomega.9b01413
• 发表时间: 2019
• 期刊: ACS Omega
• 影响因子: 4.1
• 作者: Sánchez, Oscar F.;Mendonca, Agnes;Min, Alan;Liu, Jichang;Yuan, Chongli
• 通讯作者: Yuan, Chongli