An integrated lentiviral tools manufacturing platform

The Vectalys manufacturing platform produces both non-integrative (LentiFlash) and integrative lentiviral tools from R&D to GMP grade, for scientists all over the world.  The manufacturing platform also underpins Flash Therapeutics’ internal gene therapy programs as well as its collaboration project development with partners.

Manufacturing dyptique

The Vectalys platform is a CDMO producing lentiviral technologies from R&D to therapy grade

Flash Therapeutics is built around the Vectalys manufacturing platform which benefit from production and purification processes developed and continually optimized since 2005. Through the Vectalys platform Flash Therapeutics provides a full range of products from Research to GMP grade:

Vectalys’ manufacturing platform assets:

  • For 10 years, Vectalys has compared the composition of crude and concentrated lentiviral vector products obtained from several production, concentration and purification methods. We finally defined a lentiviral vector composition which, by virtue of the high titer and purity, minimizes the deleterious target cell phenotypic changes that occur following transduction.
  • These data not only provide solutions to avoid the interference of production impurities in the transduction process but also shed a new light on apparent toxicity, wrongly associated with the lentiviral particles themselves.
     

Vectalys’ technology highlights:

  • By nature, lentiviral vectors show a wide spectrum of cell penetration,
  • Their high concentration gives them transduction efficiency with the entire cell population, 
  • Their high level of purity safeguards the physiological state of the targeted cells.

High quality lentiviral particles

Due to its proprietary and patented production process, Vectalys’ manufacturing platform provides the highest quality vectors on the market. By removing DNA impurities, and reducing empty particles level, Vectalys platform reach an excellent purity and a high titer (ratio physical particles/ transducing units). 

The purity and the concentration level provided by Vectalys come from 12 years of know-how and a unique purification process developed by Vectalys.

titer
(TU/ml)
PP/TU Ratio Specific Activity
(TU/mg protein)
Protein Removal Cell Types
>1E9 <300 >1E8  >98% Primary & stem cells

Figure 1: Quality features of lentiviral tools

A scalable and reproducible production process

The same viral product specifications are maintained from small to large-scale productions demonstrating our capability to produce the same quality vectors whatever the volume. The same quality of vector means a seamless scaling up from small to large cell number experiments. 

As a result, the same premium lentiviral tools composition can be used going from research to therapeutics.

Scalable and reproducible production process

Supply chain & project management

It goes from plasmid design to vectors’ quality controls and includes:

  • Packaging plasmids supplying  
  • Expression plasmid design, construction and production
  • Lentiviral vectors production, concentration and purification
  • Vector aliquoting
  • Quality controls:
    • Vector QCs: Titers (TU/ml) and (PP/ml)
    • Contaminants measurements: specific activities
    • Sterility
    • RCL measured by p24 detection

Vectalys ensures the full project management from project design to delivery. A report is sent at each technical step from gene synthesis to vector release. The production manufacturing delay is provided immediately upon receipt of the order. In case of any problem detected such as gene synthesis delay, the customer is immediately informed.

Project design

Depending on the project, our experts in vectorology and cell engineering advise and support scientists to find the best vector design to fit with their final expectations:

  • Lentiviral vectors or LentiFlash® particles depending on the expected expression duration
  • Cassette design that is fully customizable:
    • Gene silencing: CRISPR/Cas9, shRNA approaches
    • Gene restoration or overexpression
    • Reporter insertion
  • Vector manufacturing process:
    • Final titer: from 1E7 TU/ml et 1E9 TU/ml
    • Volume: from 1 ml et 30 ml whatever the titer

Manufacturing grade

Based on the previous developments and resulting first-class vector specifications, Vectalys is now processing the pilot production line, improving its performance in order to bring the technology to the level expected by the gene & cell therapy market, that is to say, necessary to address GMP manufacturing dedicated to phase I/II clinical trials.
In 2019, Vectalys will provide a complete offer ensuring a continuum from discovery to clinic including:

  • Packaging plasmids supplying
  • Expression plasmid design, construction, production and QCs
  • Premium vectors production, concentration, purification
  • Vectors QCs
     

Scalable GMP manufacturing capabilities

The Flash Therapeutics GMP facility, which is expected to become fully operational in 2019, is being established through a recently signed, three-year partnership with Hospital Saint-Louis, Lariboisière, Fernand Vidal (Assistance Public Hospitals of Paris AP-HP) to develop and produce gene and cell therapy drugs.