GS Xceed® Gene expression toolbox: Overview and the introduction of new tools

1. Introduction
Since its introduction to the market, continuous advancements have been made to all components of Lonza’s industry-leading GS Gene Expression System®. There are now 42 licensed products that use the GS system in their manufacture, and a review of product pipelines reveals a trend towards increasingly complex molecules. This presentation provides an introduction to the GS Xceed® system, along with a discussion on some of the recent enhancements to aid expression of complex and difficult to express proteins.
2. Theoretical
In recent years, monoclonal antibodies have been the primary protein therapeutic; however, heavily-engineered, next-generation biologics, whose domain structure is often far from that seen in Nature, now dominate early-phase pipelines. The complex nature of these molecules can mean that they are difficult to express and require new development tools to achieve economically viable concentrations and clinically relevant critical quality attributes. New tools and potential approaches to the GS Xceed® Gene Expression toolbox that will support commercially-viable expression levels of difficult to express proteins are described.
3. Results and discussion
Challenges with expression of complex molecules can be associated with the vector(s) used to insert the genes of interest. For example: (i) there may be difficulties in making vectors with greater than 2 expression cassettes, (ii) there is a lack of non-antibiotic selection markers if more than 1 vector is required, etc. To resolve this issue, Lonza has developed multi-gene GS Xceed® vectors, providing an easy way to simultaneously express 3 or 4 product (or helper) genes from a single plasmid, with a streamlined, efficient, one vessel assembly method. Review of the new system reveals an 89 to 100% and a 20 to 40% success rate for assembly of the triple- and quadruple- expression vector type respectively.
Lonza has further investigated approaches to improve expression of difficult to express proteins. Here, the impact of two approaches will be introduced, with a demonstration of their potential to positively impact product concentration.
4. Conclusions
This paper describes Lonza’s new tools and potential future approaches to simplify expression of complex proteins.

遺伝子発現システムGS Xceed® についてはこちらから
https://www.lonza.com/custom-manufacturing/development-technologies/gs-xceed-gene-expression-system.aspx


日時: 11月8日(木) 12:10 pm – 1:00 pm
会場: つくば国際展示場 | Room A
演者: Alison Porter, Ph.D., Head of Process Development Sciences, Lonza Pharma& Biotech

*本プレゼンテーションの言語は英語になります。
*本プレゼンテーションは 日本動物細胞工学会 JAACT 国際会議2018 のランチョンセミナー3として開催されます。

ロンザジャパン株式会社 受託製造開発事業部
Email: pharma-biotech-jp@lonza.com