GMP Manufacturing

As the world’s leading provider of custom gene vectors, our team has accumulated extensive knowledge in vectorology and virology, allowing us to provide optimal vector design for a variety of cell 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 deliver 60,000+ custom vectors and 30,000+ custom viruses for in vitro, ex vivo, and in vivo use. Our vector optimization capabilities include

• Rich collections of fully validated vector components:

  Backbones (clinical use compliant, especially MiniVec™), promoters (natural/synthetic, ubiquitous/tissue-specific), ORFs (including codon optimized), linkers, shRNA, and CRISPR components, etc.

• Functional screening platforms in vitro and in vivo (e.g. NHPs):

  Promoter/enhancer screening, AAV capsid evolution, coding sequence engineering, CAR antibody screening, membrane protein binding 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 herpes simplex virus (HSV).

Our USP capabilities for plasmid DNA, viral vectors, as well as IVT RNA and LNP include

• Cell line development and high-density cell culture optimization:

  E. coli, mammalian cell lines, insect cell lines

• E. coli fermentation scale-up and scale-out:

  Fermentation systems ranging from flasks to up to 100 L stirred fermenters.

• Mammalian and insect cell culture scale-up and scale-out:

  • Adherent systems: flasks, multi-layer flasks, fixed-bed bioreactors

  • Suspension systems: flasks, wave bioreactor (up to 50 L), single-use bioreactors (up to 200 L)

• Media screening and optimization:

  Antibiotic-free, serum-free, animal-free, chemically defined

• Transfection/infection optimization:

  Rep/Cap and helper plasmid optimization, plasmid DNA ratio, transfection reagent, infection MOI, cell density, etc.

• IVT RNA optimization:

  Co-transcriptional or enzymatic capping methods, nucleotide modification, dsDNA removal

• LNP engineering and optimization:

  Formulation optimization, novel formulations, antibody-conjugated LNPs, tissue-targeting LNPs

Our DSP capabilities for plasmid DNA and viral vectors include

• Harvest and lysis optimization:

  Harvest time, cell lysis method, nuclease treatment, etc.

• Purification optimization:

  • 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)

In addition to the above, our DSP capabilities for IVT RNA and LNP include

• IVT RNA linearization:

  GMP or GMP-like enzymes

• LNP encapsulation:

  Rapid phase mixing

Rigorous quality control (QC) has always been a challenge in the manufacturing of gene therapy drugs. In parallel to process development, VectorBuilder offers a comprehensive range of analytical services for developing, optimizing, qualifying, and validating in-process and release QC assays tailored to individual gene therapy vectors.

For a full list of default and optional QC assays, refer to the respective GMP product page. Additional QC services not listed may be provided upon request.

Drug stability studies are essential for ensuring that the quality of DS/DP is maintained during their shelf life. Our stability studies are performed following ICH guidelines to assess how the potency and safety attributes of the gene therapy vectors are influenced by environmental factors (e.g. pH, temperature, light) under planned storage conditions or forced degradation conditions.