Investigation of how reducing RNA-directed DNA Methylation can enhance production of therapeutic proteins in plants

研究减少 RNA 指导的 DNA 甲基化如何增强植物中治疗性蛋白质的产生

• 批准号: 543279-2019
• 负责人: Colasanti, Joseph
• 金额: $ 1.82万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=680826
• 关键词: Investigation; how; reducing; RNA; directed

Plants can be used as an efficient and cost-effective means of producing therapeutic proteins. Moreover, producing proteins such as antibodies and other medically important proteins has several advantages over recombinant cell culture approaches. These include high yields, cheap growing costs, and the ability to rapidly scale up protein production with minimal infrastructure. One obvious challenge in this process is to maximize protein production. Although transient expression of recombinant DNA constructs in plant cells has proven to produce greater yields than in stable transgenic plant lines, it often leads to silencing of the transgene and substantially reduced target protein production. Preliminary studies have shown that protein production levels can be enhanced significantly by altering the epigenetic environment of the recipient plant genome by interfering with gene silencing mechanisms. In particular, targeting the DNA methylation machinery of the cell allows for increased levels of gene expression and protein production. The goal of this project is to study the underlying mechanisms of transgene silencing, with a particular focus on ARGONAUTE proteins, which are key components of the gene silencing mechanism in plants. The partner company, PlantForm, has developed a technological platform for making therapeutic proteins in plants. The results of this project will provide a foundation for advancing these technologies towards enhanced therapeutic protein production with a goal of making the system more efficient and cost-effective.

植物可用作生产治疗性蛋白质的有效且具有成本效益的手段。此外，生产蛋白质如抗体和其他医学上重要的蛋白质具有优于重组细胞培养方法的几个优点。这些优势包括高产量、低成本的种植成本，以及以最少的基础设施快速扩大蛋白质生产的能力。在这个过程中，一个明显的挑战是最大限度地提高蛋白质产量。虽然重组DNA构建体在植物细胞中的瞬时表达已被证明比在稳定的转基因植物系中产生更高的产量，但它通常导致转基因的沉默和显著减少的靶蛋白产生。初步研究表明，通过干扰基因沉默机制，改变受体植物基因组的表观遗传环境，可以显著提高蛋白质产量水平。特别地，靶向细胞的DNA甲基化机制允许增加基因表达和蛋白质产生的水平。该项目的目标是研究转基因沉默的潜在机制，特别关注ARGONAUTE蛋白，这是植物基因沉默机制的关键组成部分。合作伙伴公司PlantForm开发了一个在植物中制造治疗性蛋白质的技术平台。该项目的结果将为推进这些技术提供基础，以增强治疗性蛋白质的生产，使系统更有效，更具成本效益。