We offer customized services for companies and institutions developing innovative genetic medicines. As a science and technology-driven platform, we provide a comprehensive approach to viral vector manufacturing, from lab-scale development to scalable bioreactor implementation, process optimization, formulation, and stringent quality control.
End-to-end solutions from R&D to commercial manufacturing
Genome engineering of the GOI (gene of interest) cassette is a dynamic process to ensure efficient gene expression, therapeutic efficacy, and AAV manufacturability. We employ the following key strategies and considerations to optimize the GOI cassette:
- Optimize ITR sequences
- Promoter selection and possibility to include enhancer or regulatory elements
- Identify cryptic splice sites, cryptic poly A sites
- Intron inclusion to stabilize mRNA
- Codon optimization to improve translation efficiency
- CpG island optimization
- Payload corrections
- Reverse package mitigation to avoid DNA impurities in AAV production
- Prioritize safety by avoiding or minimizing the use of immunogenic sequences
Our manufacturing platform is based on transient transfection of HEK293 cells in suspension, and customized state-of-the-art upstream and downstream processes.
We provide our partners:
- Technology transfer
- Lab-scale viral vector manufacturing
- Implementation of scalable single-use bioreactors technologies at 2-liter scale, enabling collection of initial yield and purity data specific to the construct. Process development needs are identified before future scale-up to pilot 50-liter scale
- Process design and selection of fit-for-purpose upstream and downstream processing technologies
- Characterization and optimization of upstream and downstream processes
- Formulation of drug product
- Scale-up development in 50-liter bioreactors based on previous stages. Material supplied can be used to complete research and GLP preclinical studies
- Assay implementation and quality control testing required for batch release
A DINAMIQS project manager and cross-functional team will help you meet your objectives, providing you with high quality vectors while minimizing process changes to de-risk and accelerate timelines.
We provide valuable input in the design and development of customizable GMP-compatible processes. Acting as a single service partner, we develop scale-up strategies to ensure a seamless transition between the different phases of your project, from early development to the manufacturing of GMP material for Phase I/II clinical studies. We ensure your process is robust, scalable, cost-effective and reproducible.
Our upstream development capacities integrate:
- Media and feed optimization for batch production
- Chemically defined medium, animal component-free
- Single-use technologies
- High viral titer, suspension cell line
- High viable cell density
- Adenovirus-free, triple plasmid transfection
- Optimized cell lysis
- DNA digestion with GMP-compatible endonuclease
- Scalable harvest and clarification operation
AAV purification is critical to ensure a high-level of product safety, including purity and potency. Our downstream development capacities integrate:
- Bioprocess filtrations (normo- or tangential flow filtration)
- Column and membrane chromatography (affinity, ion exchange, hydrophobic interaction, desalting, multimodal)
- Density gradient ultracentrifugation using Iodixanol and/or CsCl
- Design and implementation of single-use technologies
- Final filtrations with formulation and sterile filtration
- Customized fill and finish
AAV vector characterization and quality control
Analytical characterization and quality control of rAAV vectors is crucial at every stage of development and manufacturing. Our robust, accurate and reproducible analytical methods accelerate process development and ensure the quality of our manufactured vector products.
We offer a full analytical service package tailored to your gene therapy product, including:
Strength and quantification
- PCR-based vector quantification: qPCR – ddPCR
- We perform ITR-based AAV quantification and offer method development and implementation for your gene of interest sequences for quantification.
- Total capsid ELISA for all common serotypes
Potency vector transduction and infectivity
- Infectivity (TCID50 method)
- Transduction by FACS analysis (applicable to fluorescent reporter vectors)
- Expression of transgene mRNA (RT-qPCR)
- Development of customized cell-based potency assays
Purity, identity and characterization
- Protein purity and identity by SDS-PAGE/Western blotting
- Capsid protein identity by SYPRO Orange Differential Scanning Fluorimetry (protein melting temperature analysis)
- Genome integrity by alkaline gel electrophoresis
- Vector sequence identity and genome heterogeneity by long-read sequencing and bioinformatics analysis
- Particle size distribution/aggregation by dynamic light scattering (DLS)
- Empty and full AAV particle ratios by mass photometry, qPCR/ELISA and SLS-UV/VIS
- HEK 293 host-cell protein ELISA
- Bacterial endotoxin test (LAL kinetic turbidimetric method)
- Residual host-cell and plasmid DNA (qPCR-based quantification)
Our integrated servicesDownload the brochure
- At the laboratory scale (up to 0.5-liter) we engage in manufacturing small quantities of viral vectors. This phase is crucial for an early evaluation of the yield and purity of different viral vector constructs, and early optimization of the USP conditions. Since a very early stage we use single-use materials and fully GMP compatible processes: including chemically defined medium and animal-free components.
- 2-liter scale bioreactor technologies are used to perform methodical upstream and downstream process development. We establish improved cost-effective manufacturing processes that meet quality specifications in a reproducible and scalable manner.
- Scale-up development in a 50-liter bioreactor is essential for producing large quantities of vectors. The products supplied support proof-of-concept research and GLP toxicology studies.
- We support our clients in every step from cGMP manufacturing to commercial production up to 1000-liter, delivering patient-ready product.
- We implement assays and conduct rigorous internal quality control testing throughout all manufacturing processes. This is essential for ensuring the consistency, purity, and safety of the viral vector batches, meeting the required standards for batch release.
Located in Schlieren-Zurich Bio-Technopark, Switzerland, our facilities include a fully operational, 13,000-square-foot state-of-the-art R&D facility dedicated to process development, manufacturing up to 50-liter scale and analytical testing. DINAMIQS is currently building a 26,000-square-foot GMP facility that can produce viral vectors at 500-liter scale.