The crucial first step in setting up GMP manufacturing of a gene therapy drug is to develop a production process tailored to the clinical goals of the therapy. VectorBuilder has a dedicated process development team that is highly experienced in developing optimal manufacturing processes for GMP-grade gene therapy vectors. We consider many factors in our process development, including biological properties of the vector, quality and safety requirements, production quantity and scalability needs, regulatory requirements in the intended market, and the customer’s cost and timeline target.
Our process development services include:
As the world’s leading provider of vector cloning and virus packaging services, our team has accumulated extensive knowledge in vectorology and virology, allowing us to provide optimal vector design for a variety of basic research and gene therapy applications. We have created a myriad of vector designs for our customers that are effective, targeted, safe and affordable. Every year, we design and clone >30,000 custom vectors and package >10,000 custom viruses for in vitro, ex vivo and in vivo use. In addition, our strong expertise in BAC and YAC recombineering allows us to engineer large viral genomes for novel viral vector development. We have also established large-scale screening platforms utilizing high-complexity library construction technology and NGS to screen for optimal vector designs. Our vector optimization capabilities include:
Rich collections of fully validated vector components
Backbones, promoters (constitutive, tissue-specific, inducible, synthetic), ORFs, linkers, tags, shRNA and CRISPR target site libraries, etc.
Large-scale screening platforms
Tissue-specific promoter/enhancer screening, capsid evolution, shRNA screening, CRISPR screening, Rep/Cap promoter optimization, CAR antibody screening, etc.
Viral genome engineering
De novo construction of novel viral vectors, including utilizing BAC and YAC recombineering to build vectors containing large viral genomes such as coronavirus and herpes simplex virus (HSV).
Upstream Process Development (USP)
Our USP capabilities for plasmid DNA and viral vectors include:
Cell line development
E. coli, mammalian cell lines, insect cell lines
E. coli fermentation scale-up and scale-out
Fermentation systems range from flasks to up to 50 L stirred fermenters.
Mammalian and insect cell culture scale-up and scale-out
- Adherent systems: flasks, Cell Factory, fixed-bed bioreactors
- Suspension systems: flasks, single-use bioreactors (20 L, 50 L, 200 L)
Media screening and optimization
Antibiotic-free, serum-free, animal-free, TSE/BSE-free, chemically defined
High-density cell culture optimization
E. coli, mammalian cells, insect cells
Rep/Cap and helper plasmid optimization, plasmid DNA ratio, transfection reagent, infection MOI, cell density, etc.
Downstream Process Development (DSP)
Our DSP capabilities for plasmid DNA and viral vectors include:
Harvest and lysis optimization
Harvest time, cell lysis method, nuclease treatment, etc.
- Chromatography: size exclusion, ion exchange, affinity, mixed mode
- Gradient centrifugation: sucrose, CsCl, iodixanol
Clarification, concentration and buffer exchange
UF/DF (tangential flow, hollow fiber, depth filtration)