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

基本信息

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

项目摘要

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.

植物可以用作产生治疗蛋白的有效且具有成本效益的手段。此外，与重组细胞培养方法相比，产生抗体和其他重要蛋白质等蛋白质具有多个优点。这些包括高产，廉价的增长成本以及通过最少的基础设施快速扩大蛋白质生产的能力。在此过程中，一个明显的挑战是最大化蛋白质产生。尽管事实证明，植物细胞中重组DNA构建体的瞬时表达比稳定的转基因植物系的产量更大，但它通常导致转基因沉默，并大大降低靶蛋白的产生。初步研究表明，通过干扰基因沉默机制，可以通过改变受体植物基因组的表观遗传环境来显着提高蛋白质的产生水平。特别是，靶向细胞的DNA甲基化机制可以增加基因表达和蛋白质产生的水平。该项目的目的是研究转基因沉默的潜在机制，特别关注Argonaute蛋白，这是植物中基因沉默机制的关键组成部分。合作伙伴公司PlantForm开发了一个技术平台，用于在植物中生产治疗蛋白。该项目的结果将为这些技术促进增强治疗性蛋白质产生的基础，以使系统更有效和成本效益。