Cambridge Healthtech Institute’s Fourth Annual
Optimizing Protein Expression
Enhancing Expression Systems
Part of the Tenth Annual PEGS: the essential protein engineering summit
May 7-8, 2014 | Seaport World Trade Center| Boston, MA
When expressing proteins, there are a variety of expression systems to choose from. CHO is seen as the ‘king’ in the industry, but does it meet all needs of rapid production and budget constraints? This meeting will explore “Optimizing Protein Expression” through understanding and enhancing expression systems, and will especially focus on CHO cells and other mammalian systems, E.coli and baculovirus. Other host systems, such as yeast and algae, will be touched on as well.
Along with case studies, the meeting will feature experts who reveal the underlying mechanisms and insights into the varying systems in order to enhance protein expression. Comparing and contrasting systems will also be featured to provide greater understanding of how these systems function within the context of the results achieved. Learn the latest protocols and see how protein science leaders are enhancing expression systems to reach greater productivity.
Day 1 | Day 2 | Download Brochure
WEDNESDAY, MAY 7
7:00 am Registration and Morning Coffee
8:00 Chairperson's Opening Remarks
8:10 Engineering Recombinant Proteins for Improved Manufacturability in CHO Cells
Sujeewa D Wijesuriya, Ph.D., Senior Scientist, XOMA (US) LLC
Case studies will be presented that identify manufacturability issues with two recombinant proteins. First, we greatly improved expression of CAB-2, a hybrid recombinant protein, by eliminating unproductive mRNA coding sequences. Second, we established that light chain was responsible for poor expression and high aggregate levels in a recombinant antibody. Light chain shuffling yielded an antibody with high binding affinity, and improved expression and product quality.
8:40 Development and Use of a High-Yielding, High-Throughput CHO-Based Transient Expression System
Robert Roth, Ph.D., Associate Principal Scientist, Innovative Medicines, Discovery Sciences, AstraZeneca
9:10 Aeration Strategies and the Control of Interfacial Stress in Mammalian Cell (CHO) Culture
Daniel G. Bracewell, Ph.D., Reader, Biochemical Engineering, University College London
Understanding gas transfer is critical to the design and scale-up of bioreactor conditions with landmark events being the use of stirred tank reactors for penicillin in 1944 and discovery of surfactants for mammalian cell culture in 1968. The advent of biosimilars and the commodification of antibodies challenges the depth of our understanding. We present our recent results on the subject in this context.
9:40 Estimation of Metabolic Rewiring in CHO Cell Culture Using Combined 13C-Metabolic Flux Analysis
Woo Suk Ahn, Ph.D., Research Associate, Bioinformatics and Metabolic Engineering, Massachusetts Institute of Technology (MIT)
13C-Metabolic flux analysis (13C-MFA) is a powerful methodology to quantify intracellular metabolism using stable isotopic tracers. We introduced multiple tracers in parallel to quantify CHO central metabolism. Here, we revealed metabolic rewiring from growth to non-growth phase. In addition, by design of multiple isotopic tracers, we achieved high accuracy and resolution of flux values. This technology enables us to identify and optimize CHO cellular metabolism.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
» 11:10 KEYNOTE PRESENTATION: The Production of Complex Proteins in Drug Discovery: Challenges & Solutions
René Assenberg, Ph.D., Research Investigator, Novartis Pharma AG
Recently there’s been a trend towards greater complexity of proteins targeted for drug discovery. The production challenges of such proteins require a range of different tools, including different expression systems, novel protein engineering and analytical approaches. This talk will outline some of the challenges our group faces in this area, with emphasis on glycoproteins and protein complexes, as well as the solutions we deploy.
11:40 FEATURED PRESENTATION: Protein Expression Technologies - Evolution or Revolution?
Lorenz Mayr, Ph.D., Vice President & Global Head, Reagents & Assay Development, AstraZeneca
I will give an overview of protein expression at AstraZeneca Pharmaceuticals, including: An overview of established protein expression technologies; Novel trends and demands for proteins in hit discovery and lead optimization; Novel technologies and trends for protein expression in drug discovery research; Case studies for difficult-to-express proteins and protein complexes; Finding the balance between in-house efforts and outsourcing, and summary and outlook.
12:10 pm Sponsored Presentation
Speaker to be Announced
12:25 Sponsored Presentation (Opportunity Available)
12:40 Luncheon Presentation I: Engineering of Genes, Proteins and Pathways for Systematic Optimization of Therapeutic Protein Production
Mark Welch, Ph.D., Director, Gene Design, DNA2.0 Inc.
1:10 Luncheon Presentation II (Sponsorship Opportunity Available)
1:40 Session Break
2:00 Chairperson's Remarks
2:05 A Novel Baculovirus Vector for Production of Non-Fucosylated Recombinant Glycoproteins
Donald Jarvis, Ph.D., Professor, Molecular Biology, University of Wyoming
The inability to provide human-type protein glycosylation patterns has precluded the use of baculovirus-insect cell systems for therapeutic glycoprotein production. Recent glycoengineering efforts have advanced the platform through the creation of improved systems that can produce recombinant glycoproteins with human-type, complex, terminally sialylated N-glycans. We produced the first baculovirus-insect cell systems capable of producing non-fucosylated recombinant glycoproteins, including antibodies, and characterized their capabilities.
2:35 Insect Cell Culture for Rapid GMP Manufacturing of Seasonal and Pandemic Influenza Vaccines
Nikolai Khramtsov, Ph.D., Associate Director, Upstream Development, Product Realization, Protein Sciences Corp.
We developed a universal process for the generation of recombinant baculovirus banks for seasonal and pandemic influenza antigens, as well as for the expression and purification of these antigens at large scale. Less than 30 days is required for the introduction of new antigens to GMP manufacturing. Influenza seasonal vaccine Flublok, containing three different hemagglutinin antigens, can be manufactured during two months.
3:05 The Impact of Scalable Transfection: Maximizing CHO Antibody Production Using Flow Electroporation to Accelerate Development Timelines
James Brady, Ph.D., MBA, Director, Technical Applications, MaxCyte
CHO transient gene expression (TGE) greatly accelerates antibody development by eliminating the need to change cell backgrounds during scale up to biomanufacturing. Flow electroporation enables scalable transient transfection of a variety of CHO cell lines producing sufficient quantities of antibodies for early and mid-stage antibody development. The production of antibody titers >1g/L yielding multiple grams of antibody from a single transfection, as well as the rapid generation of stable CHO cell lines will be discussed.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:20 Problem Solving Breakout Discussions
5:20 Networking Reception in the Exhibit Hall with Poster Viewing
6:30 End of Day
Day 1 | Day 2 | Download Brochure