Cell and gene therapies are on the brink of transforming the pharmaceutical industry, presenting unique challenges such as ensuring the quality and consistent supply of reagents. Reagents play a crucial role in various stages of cell therapy development, from cell isolation and expansion to gene editing and characterization. Any inconsistency or variation in the quality of reagents can affect the reproducibility, efficacy, and safety of cell therapy products. GenScript, a leading biopharmaceutical supplier, addresses these challenges with tailored solutions. Our stringent quality control measures and robust supply chain management ensure consistent, high-quality reagents for both small and large-scale manufacturing. Additionally, GenScript provides phase-specific cell therapy solutions, offering flexibility, expertise, and capacity to support projects at any stage. This accelerates the therapeutic pipeline from early-phase research to clinical applications. These efforts aid successful IND submissions and clinical trials, facilitating the translation of therapies into clinical practice.

Our upcoming webinar will cover the following topics:

• Exploring cGMP Cell Isolation Reagents and Automation Solutions

• Overview of cGMP sgRNA, Cas9 & HDR Template Options

• Overview of cGMP Neoantigen Peptides Services

• Outline to cGMP Plasmid and Vector Packaging Services

• Insights into cGMP Manufacturing Expertise and Capacity

Don’t miss this opportunity to improve your processes and make your life easier!

mRNA vaccines represent a pivotal innovation in prophylactic healthcare, offering a rapid response to emerging infectious diseases. Leveraging the cellular machinery to produce antigenic proteins, these vaccines induce robust immune responses without introducing live pathogens. Recent developments have focused on optimizing mRNA stability, delivery systems, and targeted immune activation. This presentation will delve into the molecular design strategies that enhance translational efficiency and immunogenicity while ensuring safety and tolerability. We will also explore the real-world impact of mRNA vaccines, evidenced by their critical role in combating the COVID-19 pandemic. The session aims to provide a comprehensive overview of current challenges, potential solutions, and future directions in mRNA vaccine technology. In addition, I will review the advanced solutions offered by GenScript for vaccine development, from gene sequence and codon optimization to plasmid production and linearization to optimized mRNA encapsulated in LNP and ready for delivery.

Learning Objectives: 

1. Review the advantages of mRNA vaccines compare to other types.

2. Summarize the typical procedure for producing mRNA vaccine.

3. Review considerations for the optimization of mRNA vaccines.

Human induced pluripotent stem cells (hiPSCs) are a powerful tool for innovative approaches, such as drug discovery, in vitro disease modelling, or regenerative therapies. However, such procedures require high cell numbers to be sufficiently applicable, a criterion that is hard to satisfy with traditional 2D culture methods. Stirred-tank bioreactors on the other hand offer a 3D culture environment suitable to provide, control, and maintain optimal growth conditions for the cell of choice. In this webinar, an expert by Eppendorf will present how stirred-tank bioreactors can be utilized to systematically optimize process parameters of a hiPSC culture in a step-by-step process; an approach that led to a more than 10 × increase in cell density (almost 35 million cells/mL) compared to uncontrolled conditions while stem cell features and viability were retained.

Learning Objectives: 

1. Identify the potential and challenges associated with induced pluripotent stem cells.

2. Review the basic principles of a stirred-tank bioreactor.

3. Summarize how stirred-tank bioreactor-based stem cell culture can be optimized through precise parameter control.

Join this year's poster presenters in the Poster Hall during the Poster Discussion, Wednesday, April 3rd, from 10:00 AM –11:00 AM PST, to chat live about their posters and latest research and findings.

Cultured mammalian cells, particularly Chinese hamster ovary (CHO) cells are widely used in the biotechnology industry for production of a wide range of therapeutics, predominantly monoclonal antibodies and other therapeutic proteins. Recently, there has been increased interest in the production of therapeutic carbohydrates such as heparin and heparan sulfates and in control of protein glycosylation as we enter the world of biosimilars.

In this presentation, I will provide an overview of the history of biotherapeutic production and highlight a range of contributions to the field from my laboratory including studies of hyperosmotic stress, understanding manufacturability, and evaluating factors that control productivity using a range of ‘omics technologies in antibody producing CHO cell lines. I will further discuss metabolic engineering of CHO cells and murine mastocytoma cells to produce a bioengineered heparin.

Learning Objectives: 

1. Gain familiarity with the history of biomanufacturing and the role of mammalian cells in production of biotherapeutics.

2. Identify the challenges in producing a non-animal-derived (aka Bioengineered) heparin.

3. Recognize the role that biosimilars play in the current biotherapeutic landscape.

Gene therapy has revolutionized the field of medicine, and it has the potential to cure a wide variety of genetic disorders. Gene therapy involves the introduction of a functional gene into the patient's cells to replace the missing or defective one. The two main technologies used for gene therapy are viral-based and non-viral gene editing.

The primary advantage of viral-based gene editing is that viruses are highly efficient at transferring genes into cells. However, there are risks associated with viral-based gene therapy, such as the potential for the virus to cause immune system reactions or to integrate into the patient's DNA in harmful ways.

Non-viral gene editing, such as CRISPR, has emerged as a promising alternative to viral-based gene therapy. CRISPR is a revolutionary gene-editing technology that allows scientists to modify genes with unprecedented precision and ease. Non-viral gene editing has several advantages over viral-based gene therapy, including a lower risk of immune system reactions and less potential for the genetic material to integrate into the patient's DNA.

The impact of gene therapy and gene editing technologies has been significant in the medical field. Over 32 gene and cell therapies have been approved by the FDA so far with significant impact on disease outcome.

The quality of the reagents used for development of therapies is critical for the success. Regardless of the type of gene therapy you are developing, GenScript has an extensive solution of high-quality services and products that can fulfill you development needs. In this webinar we will discuss the GenScript solutions for discovery, lead generation and optimization and pre-clinical and clinical development of gene therapies.

Learning Objectives: 

1. Learn about the methodologies available for in-vivo gene editing.

2. Learn about the critical steps for each technology and how to best optimize.

3. Discover the complete toolbox of technologies available from GenScript.

Quantifying critical quality attributes accurately and precisely is an important aspect of regulatory compliance. There is greater demand to optimize processes by integrating advanced analytical tools that maximize quality, safety, and efficacy of biotherapeutics.

Kalhari Silva, from Custom Biologics, will provide insight on how her team designs and establishes methods suitable for comparability studies that allow for their future use in qualified or validated GMP lot release and stability testing. Custom Biologics is a leading large and small molecule CRO that provides highly specialized, GLP-compliant, bioanalytical development, validation and testing services in support of pre-clinical and clinical stages of pharmaceutical drug development.

Three case studies involving the binding of therapeutic monoclonal antibodies to their cellular receptors and soluble targets that contribute to the assessment of their critical quality attributes will be discussed. Their approach to generate reproducible and high-quality data will focus on, but will not be limited to, biosensor selection, ligand/analyte orientation, choice of buffer system, ligand immobilization and troubleshooting tips.

Design of Experiments (DOE) is a powerful and pragmatic tool for optimisation but it’s not the only way. Could there be even more powerful alternatives in the age of machine learning, AI and automation?

Active learning is an artificial intelligence method that makes use of machine learning algorithms to determine the next set of experiments to be carried out.

Traditional methods for process optimization based on DOE rely on domain specific expertise of the experimenter and are subjective in their interpretation and design. Active learning methodologies can be used to iterate following on from initial DOE based experimental design and promise more systematic iteration with less need for human input. For this reason they can be particularly powerful and can pave the way for automated closed loop optimisation.

We demonstrate here the application of an active learning based framework and an LLM with a cloud based digital experiment platform capable of planning and capturing results of experiments run on lab automation. We used it to optimize miniaturized fermentation for recombinant protein production in bacteria. We performed 4 iterations which resulted in a 5 fold increase in maximum rate of protein production and 2 fold increase in protein titre. We also attained many key insights into behavior.

Nanoparticle mRNA Therapeutics has been the focus of intense research driven by the safety profile and several clinical breakthroughs. As of March 2024, there are two mRNA vaccines approved and many are in active clinical trials. The expected increase in demand for specific Nanoparticle mRNA therapeutics still poses many challenges. The current talk tries to summarize the key aspects related to Research and development needs and Chemistry, Manufacturing and Control (CMC) efforts to help this growing demand. We will primarily discuss applying the different orthogonal methods to identify, monitor and control Critical Quality Attributes (CQAs) during the process development and manufacturing process.

Learning Objectives: 

1. Review different analytical techniques for mRNA therapeutics.

2. Summarize the unique challenges in finding the Critical Quality Attributes (CQAs) for mRNA therapeutics.

3. Demonstrate knowledge about regulatory guidance around lipid nanoparticle analytical characterization.

In the slowly evolving landscape of bioprocess development and manufacturing, digital bioprocess-twins have emerged as potential accelerators. While advanced algorithms are at the heart of this endeavor, they are just one piece of the puzzle. The lecture delves into key discussion points that are integral to this paradigm shift. The foundation of accelerated process development and automated process control starts with a clever experimental design, in-time data accessibility combined with powerful modeling algorithms. The lecture will highlight the advantages of using AI and hybrid modeling, while emphasizing the other critical aspects on his journey. Several industrial relevant upstream showcases for microbial and mammalian celllines will be highlighted. Thereby, concepts to save experimental effort by up to 70% will be elaborated, and the modeling structure created in the late-stage development will be reused for real-time monitoring and control in the later stages. Also, one downstream optimization showcase for UF/DF/SPTFF will be highlighted. The talk will wrap up by presenting a future vision and emphasizing the necessity for these modeling approaches to become an integral component of student curricula.

Learning Objectives

1. Explain the pitfalls and solution paths for implementation of AI and digital twins.

2. Describe how to apply the circle of process modeling.

3. Define examples of Upstream and Downstream Optimization possibilities.

Effective process development for viral vector-based medicines is paramount for optimized process efficiency, robustness, scalability, and product quality. Well-designed processes streamline manufacturing to ensure consistent and reliable viral vector products, essential for successful advanced therapy development.

In this presentation, we will discuss how innovative process development solutions, that combine best-in-class bioprocessing expertise and state-of the-art technology with contemporary digitalization and machine-learning approaches pave the way for a highly efficient CMC pathway. How pre-defined modular building blocks and pre-established framework technologies can reduce complexity and offer adaptable resources that serve as step stone for process customization. By harnessing these methodologies, process development can significantly be expedited, process understanding can be increased and ultimately risks of failure can be mitigated.

Learning Objectives: 

1. Review the major technical hurdles when transitioning into clinical development.

2. Summarize the principles of QbD and their limitations in early process development.

3. Demonstrate how to empower process development by implementing data driven modeling.

Chimeric antigen receptor T-cell (CAR-T) therapies have emerged as a revolutionary approach in the field of hematological malignancies, offering unprecedented clinical efficacy when patients have exhausted any other treatment option. Currently, six CAR-T products are available worldwide, but many of the manufacturing challenges are yet to be addressed. In addition, a single therapeutic dose of CAR-T can cost up to USD 500K. A significant fraction of the cost is related to manufacturing the viral vector required to introduce the clinically relevant CAR construct. As such, non-viral gene delivery platforms such as electroporation or mechanoporation can potentially decrease the costs of manufacturing associated with CAR-T products. This study focused on establishing a scalable manufacturing method for CAR-T cell therapies using electroporation and a sleeping beauty transposon-transposase system employed to ensure stable integration of the CAR transgene.

Learning Objectives: 

1. Review what chimeric antigen receptor (CAR) T cell therapies are and how they are manufactured.

2. Demonstrate knowledge on the manufacturing process and which unit operations are in urgent need of optimisation to achieve cost reduction. 

3. Develop fundamental knowledge on how non-viral technologies can be used for knock-in and knock-out certain genes within the CAR-T manufacturing context. 

Self-removing affinity tags have the potential to greatly accelerate the development of new therapeutics, while providing a potentially enabling manufacturing platform for non-mAb therapeutic proteins.  One example involves the pH-controlled self-cleaving of a small intein-derived affinity tag.  In this talk, I will present our most recent work with our tag, including case studies on the purification of a variety of biosimilar candidates and potential biopharmaceutical candidates.

Learning Objectives: 

1. Review how self-removing affinity tags are an effective way to purify non-mAb proteins.

2. Summarize how basic protocols for using self-removing tags will be provided.

3. Explain how properties of the target proteins to be purified can have a significant impact on the cleaving rate.

Efficient utilisation of abundant renewable sugars and aromatic chemicals by natural or recombinant microorganisms is a key prerequisite for the economic viability of biotechnological valorisation of lignocellulosic residues. But biotechnologically relevant microorganisms rarely utilise aromatics, many lack xylose metabolism, and some prefer glucose or other available organic substrates over pentoses. To establish the utilisation or co-utilisation of renewable substrates by a cell factory, rational genetic interventions are often combined with adaptive laboratory evolution. However, comprehensive studies enabling a holistic understanding of adaptation processes primed by rational metabolic engineering and introduced synthetic genetic devices remain scarce.

The laboratory and industrial workhorse Pseudomonas putida, intensively studied for its potential to up-cycle waste lignin, was previously engineered to utilise and valorise the non-native sugars D-xylose and D-cellobiose, a glucose dimer. However, the assimilation of these substrates into the bacterial biochemical network via the exogenous pathways remained unresolved and inefficient. Here, we describe the elucidation and improvement of the semi-synthetic xylose metabolism and glucose-cellobiose co-metabolism in P. putida using computational and experimental tools. Using the multi-omics analyses, enzyme and cell growth assays, and reverse engineering, we demonstrate how the knowledge-directed metabolic engineering primed further adaptation of P. putida to xylose during laboratory evolution. Using the example of improved cellobiose and glucose co-consumption and valorisation, we also show the descriptive and predictive power of an upgraded genome-scale metabolic model constrained by kinetic and proteomic data. The findings presented here are instrumental for exploiting the semi-synthetic metabolism of renewable sugars in P. putida as well as for the understanding of bacterial adaptation to new substrates.

Learning Objectives: 

1. Review how systems metabolic engineering and laboratory evolution can be used to adapt bacteria to non-native substrates.

2. Summarize how directed engineering cuts can promote parallel evolutionary pathways towards the same phenotype.

3. Demonstrate knowledge on a new "carbon push" strategy enabling the aerobic overproduction of pyruvate from cellulosic sugars by a bacterial catalyst.