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

植物可以被用作生产治疗性蛋白质的一种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，生产抗体等蛋白质和其他医学上重要的蛋白质有几个优势。这些包括高产量、廉价的种植成本，以及以最少的基础设施快速扩大蛋白质生产的能力。这个过程中的一个明显挑战是最大限度地提高蛋白质产量。虽然在植物细胞中瞬时表达重组DNA结构物比在稳定的转基因植物系中产生更高的产量，但它通常会导致转基因沉默，并显著减少目标蛋白的产生。初步研究表明，通过干扰基因沉默机制来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生产水平。特别是，针对细胞的DNA甲基化机制可以提高基因表达和蛋白质生产的水平。这个项目的目标是研究转基因沉默的潜在机制，特别是ArgAerte蛋白，它是植物基因沉默机制的关键组成部分。合作伙伴公司PlantForm已经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动这些技术提高治疗性蛋白质生产的水平提供基础，目的是提高系统的效率和成本效益。

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.