权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Modification of a plant-based expression system for therapeutic protein production through genetic modification of endogenous plant N-glycosylation

通过内源植物 N-糖基化的遗传修饰来修饰用于治疗性蛋白质生产的植物表达系统

基本信息

批准号：
2666066
负责人：
金额：
--
依托单位：
Oxford Brookes University
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2666066
关键词：
Modification plant based expression system

项目摘要

Plant cells are a capable system for producing economically and therapeutically important proteins for a variety of applications, and are considered a safer production system than some existing hosts such as bacteria or yeasts. However, plants do not perform modifications to proteins in the same manner as mammalian cells do, which can have far reaching consequences for their safety and effectiveness. This project aims to genetically modify tobacco plants (Nicotiana tabacum) to create a plant-based system capable of fully "humanizing" proteins of interest, whilst improving safety of final product. We aim to demonstrate that the mammalian glycosylation enzymes B4GALT1, ST6GAL, GNTIV and GNTV can be expressed in plant cells, and localise to specific cisternae of the Golgi body. In instances where enzymes are more effective within specific cisternae, such as GNTIV & GNTV in the medial-Golgi and ST6GAL & B4GALT1 in the trans-Golgi. We demonstrate strategies to modify localisation to the desired cisternae by use of construct fusions with plant Cytoplasmic-Transmembrane-Stem (CTS) regions.This project addresses key areas of study for the British Biological Research Council (BBSRC) on new strategic approaches to industrial biotechnology. The project would offer an economically viable system for the production of high value renewables and therapeutics in a plant model organism as a low immunogenic alternative to existing systems, developed by fundamental manipulation of plant biology. This project aligns also with the BBSRC priority of 'World Class Underpinning Bioscience' as glycosylation is a critical aspect of cell functionality.

植物细胞是一种能够生产多种应用的经济和治疗上重要的蛋白质的系统，并且被认为比某些现有宿主（例如细菌或酵母）更安全的生产系统。然而，植物不会像哺乳动物细胞那样对蛋白质进行修饰，这可能对其安全性和有效性产生深远的影响。该项目旨在对烟草植物（Nicotiana tabacum）进行基因改造，创建一个基于植物的系统，能够完全“人性化”感兴趣的蛋白质，同时提高最终产品的安全性。我们的目的是证明哺乳动物糖基化酶 B4GALT1、ST6GAL、GNTIV 和 GNTV 可以在植物细胞中表达，并定位于高尔基体的特定池。在酶在特定池内更有效的情况下，例如内侧高尔基体中的 GNTIV 和 GNTV 以及反式高尔基体中的 ST6GAL 和 B4GALT1。我们展示了通过使用与植物细胞质跨膜干（CTS）区域的构建体融合来修改所需池的定位的策略。该项目针对英国生物研究委员会（BBSRC）关于工业生物技术新战略方法的关键研究领域。该项目将提供一个经济上可行的系统，用于在植物模型生物中生产高价值的可再生能源和治疗药物，作为现有系统的低免疫原性替代品，通过植物生物学的基本操作开发。该项目也符合 BBSRC 的“世界级基础生物科学”优先事项，因为糖基化是细胞功能的一个关键方面。