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Informa
Jun 12
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7:00am - 8:00am 60 mins
Breakfast & Registration
8:00am - 8:15am 15 mins
Chairperson's Remarks
8:15am - 8:45am 30 mins
Developments in Host Cell Engineering to Improve Quality & Growth
Two Cytoplasmic Ubiquitin E3 Ligases and an ER Protease Mediate ER-associated Degradation of Unfolded Antibody Heavy Chains
  • Shahram Misaghi, PhD - Scientist, Genentech
8:45am - 9:15am 30 mins
Developments in Host Cell Engineering to Improve Quality & Growth
Enhancement of cell line productivity by cell engineering, media additives and vector design.
  • Boaz Tirosh - Associate Professor of Pharmacology, Institute for Drug Research, The Hebrew University of Jerusalem, Faculty of Medicine
9:15am - 9:45am 30 mins
Info
Developments in Host Cell Engineering to Improve Quality & Growth
Targets for CHO cell engineering: Distinguishing “drivers” and “passengers”
  • Alan Dickson, Phd - Director of Centre of Excellence in Biopharmaceuticals (COEBP), Professor of Biotechnology, University of Manchester

How do we select the appropriate genes to edit to enhance CHO cell properties? Background literature suggest some that are obvious but in the environment of the cell the multiplicity of interactions makes successful selection unpredictable. Using model CHO cell systems, this presentation will focus on approaches and technologies that screen for genes with greater likelihood of presenting the “drivers” that control CHO cell suitability for production of recombinant therapeutics.

9:45am - 10:30am 45 mins
Networking Refreshment Break in Poster & Exhibit Hall
10:30am - 11:00am 30 mins
Info
Applications in Genome Editing in Cell Line Development
CRISPR/Cas9 Platform Development for Drug Target Discovery and Validation
  • Benjamin Haley - Senior Scientist, Genentech, Inc

The genomics era of biology has provided the scientific and medical community with an exquisitely-detailed view of the genetic complexity underlying human disease. While technical advances have made genome sequencing cheaper, more robust, and faster than ever, similarly effective technologies that enable basepair-by-basepair manipulation of DNA in human cells to model disease or therapeutic intervention have only recently been described. Specifically, adaptation of CRISPR/Cas9, a bacterial genome defense system, for eukaryotic molecular genetics has ushered in a new phase of the genomics revolution. Here, I will present the framework of a CRISPR/Cas9-based platform for drug target discovery and validation and how this platform can be exploited for single gene to genome-scale experimentation.

Key takeaways:

1. Modifications of CRISPR/Cas9 enable a wide range of genetic manipulations in human cells.

2. CRISPR/Cas9-mediated cell line engineering can be applied to study one or all human genes within a single experiment.



11:00am - 11:30am 30 mins
Info
Applications in Genome Editing in Cell Line Development
Engineering CHO cells with enhanced traits with multiplex genome editing
  • Nathan Lewis, PhD - Assistant Professor, Department of Pediatrics, University of California, San Diego

highlights:

1. Genome sequencing efforts have provided a parts-list for CHO cells

2. CRISPR has enabled the rapid engineering of cells

3. We have developed cell lines with multiple genetic changes to improve CHO cell growth and product quality

11:30am - 12:00pm 30 mins
Info
Applications in Genome Editing in Cell Line Development
Improving Biopharmaceutical Production of CHO Cells using Targeted Genome Engineering Tools
  • Kevin Kellner, National Institute for Cellular Biotechnology, Dublin City University

MicroRNAs with their ability to target hundreds of genes have been shown to play an essential role in the behaviour of cells. Therefore, the depletion or overexpression is a vital tool for the improvement of bioprocess attributes of CHO producer cell lines concerning productivity, growth or longevity. With the development of newer and better genome engineering tools we considered the depletion or complete deletion in several cell lines.

12:00pm - 12:30pm 30 mins
Info
Spotlight Presentation
An all-in-one system for single cell printing and whole well imaging in cell line development
  • Ian Taylor - Director, Solentim

Currently, scientists in cell line development and cell engineering struggle with limiting dilutions and FACS for isolating single cells. This is then followed by a separate whole well imaging step to provide assurance of clonality.
The new VIPS system streamlines the workflow to combine single cell printing and whole well imaging into one easy to use system.
Data will be presented with commercial lines to illustrate high seeding and cloning efficiencies.
Additional workflow benefits will also be presented.

12:30pm - 1:45pm 75 mins
Luncheon Round-Table Discussions in Poster & Exhibit Hall
1:45pm - 2:15pm 30 mins
Info
Applications in Genome Editing in Cell Line Development
Advanced technologies for reconstitution of multi-protein complexes
  • Arnaud Poterszman, PhD - Research Director, IGBMC Illkirch, (CU Strasbourg) France

Many cellular processes are accomplished through the assembly of multiple proteins acting in concert to catalyze specific activities. Moreover, multiprotein complexes by themselves constitute powerful reagents as biologics for the prevention and treatment of human diseases. Although technologies tremendously improved, production of recombinant multiprotein complexes often remains challenging and requires considerable investments, particularly for large complexes that might be incompletely characterized.

We will illustrate how genome editing technologies (such as the CrispR/Cas9 approach) allow to isolate complexes produced from their natural genomic environment for detailed analysis of their composition and how the baculovirus expression vector system (BEVS) has turned out to be particularly powerful for reconstitution of multisubunit complexes. We will comment on current developments and their potential to accelerate protein complex research: use of Lambda red recombination for improvement of the baculoviral genome, vector development for parallel expression/co-expression screening and Tandem Recombineering by SLIC cloning and Cre-LoxP fusion to generate multigene expression constructs. As model systems, we will use human multi-protein complexes involved in the regulation of gene expression such the pTefb cdk/cyclin pair, nuclear hormone receptor complexes or the 10 subunits transcription/DNA repair complex TFIIH.

Key words:

CRISP/Cas9, Recombinant protein production, Baculovirus, multi-gene expression, multiprotein complex, synthetic biology  

2:15pm - 2:45pm 30 mins
Cell Bank Characterization
LIVCA and Cell Banking Characterization
  • Benson Li - Associate Principal Scientist, Merck
2:45pm - 3:15pm 30 mins
Info
Spotlight Presentation
Novel Transposase Tools for Cell-Line Engineering
  • Ferenc Boldog, PhD - Director, Cell Line Development and Cell Banking, ATUM

We have developed powerful cell engineering tools from novel hyperactive transposases and their cognate transposons.  The system facilitates rapid development of high productivity, stable CHO and other mammalian cell lines in engineered genetic backgrounds. The valuable features of the system, and characterization of its performance will be illustrated with specific cell line development and cell engineering case studies.

3:15pm - 4:00pm 45 mins
Networking Refreshment Break in Poster & Exhibit Hall
4:00pm - 4:30pm 30 mins
Info
Keynote Presentations
New parts and systems for CHO cell synthetic biology
  • David James - Professor of Bioprocess Engineering, Chemical and Biological Engineering, University of Sheffield

Synthetic biology based on the “Design-Build-Test-Learn” cycle offers a new paradigm for CHO cell engineering, where it is possible to engineer the host cell factory in a product specific manner via combinatorial “tuning” of discrete cellular synthetic processes and directed engineering of the synthetic capacity and process performance of the host cell itself. Using this approach permits “one-size-fits-all” genetic vectorology and mechanistically blind screening of transfected cells to be replaced with tailored design and construction of specifically fit-for-purpose cell factories. This engineering design system relies upon a toolbox of synthetic parts with user-defined functionality and platform technologies that work in synchrony to enable product manufacturability. I describe our systematic approach, based on a combination of ‘omic datastreams and modeling, to create new synthetic genetic parts and cell engineering strategies that permit us to control core cellular synthetic processes such as transcription, translation and polypeptide folding/assembly in a high-capacity host cell chassis.

4:30pm - 5:00pm 30 mins
Info
Keynote Presentations
Genomic Stability of CHO – Karyotype Variance of Host Cell Lines, Recombinant or Selected Cell Pools and Subclones
  • Martina Baumann, PhD - Researcher, Austrian Centre of Industrial Biotechnology (ACIB)

Martina Baumann1, 2, Sabine Vcelar1, Michael Melcher1, 2, Vaibhav Jadhav1, Norbert Auer1, Anja Puklowski3, Till Wenger3, Nicole Borth1, 2

1Austrian Centre of Industrial Biotechnology, Vienna, Austria

2University of Natural Resources and Life Sciences, Vienna, Austria

3Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

Chromosomal rearrangements are a common phenomenon in rapidly growing cell lines such as Chinese hamster ovary (CHO) cells. Using Chromosome counting and chromosome painting we show that i) different host cell lines are distinguishable by marker chromosomes ii) there is high variability in chromosome counts as well as karyotype variants within each population, be it host cell line, selected pool or subclone; iii) subcloning does not contribute to a more homogenous karyotype. To conclude, genomic variance is high in all populations of CHO cell lines as it occurs with each division, making subcloning an unsuitable tool to enhance population homogeneity.

5:00pm - 6:00pm 60 mins
Networking Reception