A unique translational expertise in gene therapy

Health
Summary
  • Viral vectors manufacturing
  • Vector production center
  • Immune monitoring analyses
  • Gene Therapy Immunology Core
  • Preclinical analysis
  • Preclinical analysis core

    • Our experts in viral vector production work in the gene therapy laboratory in Nantes to support you in the development of new drugs.

    CAPACITÉS’ teams in monitoring host immune response, preclinical assays and viral vector production offer a complete range of support for the development of drug candidates.

    With internationally recognized know-how in the field of gene therapy, our experts offer the responsiveness of a CRO (Contract Research Organization) in the discovery and development phases of gene therapy products.

    Services

    Proof of concept

    Preclinical data

    Manufacturing

    Preclinical assays

    Technology platforms

    Viral vectors manufacturing

    In close collaboration with TaRGeT UMR 1089 gene therapy laboratory (UMR INSERM-Nantes Université), we propose the development of processes for the production and characterization of viral gene transfer vectors derived from adenoviruses and AAV. These vectors are intended for applications ranging from basic research to preclinical trials.

    In a nutshell
    AAV vectorsvector plasmidsanalysis processesR&D

    Production of recombinant AAV vectors

    • Testing and proof of concept
    • Production by homologous recombination or amplification
    • Hybrid vectors (ITR AAV2)
    • Serotypes 1, 2, 3, 4, 5, 6, 7, 8, 9, rh 10
    • Variants (2i8, DJ, …)
    • Single-stranded and self-complementary rAAV
    • 400 lots per year

    Custom construction of vector plasmids

    • Strategy and design of plasmids
    • Production of plasmids
    • Molecular cloning
    • Amplification de plasmides pour la production de vecteurs

    Development of analysis processes and techniques

    • Development of GMP compatible processes for small/medium scale manufacturing of viral vectors (rAAV)
    • Evaluation of innovative platforms for viral vector amplification (upstream, USP) and purification (downstream, DSP) processes
    • Development of production processes in adherent and suspension cells
    • Development of adapted analytical methods: purity, identity, titre, infectious power
    • Production and characterization of rAAV batches for preclinical efficacy, dose assessment and toxicity studies
    • ICH S6 Directive
    • Biocompatibility studies in final GMP containers

    R&D

    • Research center dedicated to innovation in viral vector production
    • Development of high-performance custom processes for vector production
    • Improved efficiency of rAAV genome wrapping
    • Development of analytical tools based on next generation sequencing and bioinformatics
    • Characterization of genomes and contaminant residues from viral vector manufacturing processes

    Vector production center – CPV

    The research teams and the vector production center of TaRGeT UMR 1089 Gene therapy laboratory work together to ensure reliable, high-quality production and characterization of viral vectors. They can also develop custom analytical tests and new innovative characterization tests.

    In a nutshell
    Upstream technologiesDownstream technologies

    Upstream technologies

    • HEK293 adherent cells – Cellstacks® vessels (CS) – Up to 24 CS10 per batch for small and medium rAAV production
    • Sf9 cells / BEV platform from 2 to 50 liters per batch for small and medium productions of rAAV
    • HEK293 cells in suspension. Process development phase, cell line screening…
    • 2 benchtop bioreactors: Biostat® B benchtop for 2L/10L scale

    Downstream technologies

    • Clarification: deep filtration, low speed centrifugation, HP homogenization (C55 cell disrupter)
    • Purification: Ion exchange column (IEX), immuno-affinity chromatography (Akta Ready, Akta Pilot, Akta Purifier
    • Akta Explorer), density gradient ultracentrifugation, TFF (KR2i – Spectrum Labs)
    • Formulation, filling in cryovials (multipette/X-Stream®)

    Immune monitoring analyses

    Experts in the monitoring of host immunity in gene therapy protocols, we provide analyses for monitoring immune responses directed against the vector and against the transgene product. We assist in the development of your gene therapy products, from the research project to toxicology studies and clinical trials.

    In a nutshell
    Humoral immunityCellular immunitySample preparation

    Humoral immunity

    • Search for neutralizing factors (AAV, Adenovirus)
    • Detection of anti-AAV and anti-transgen antibodies
    • Cytokines quantification

    Cellular immunity

    • Assessment of the T cell response
    • Multiparametric cell phenotyping

    Sample preparation

    • Isolation of plasma or serum
    • Cell isolation (from whole blood, spleen, lymph nodes, bone marrow)

    Tests available for :

    • Different vectors: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV8, AAV9, AAV10 and Adenovirus
    • Several types of samples: PBMC (Peripheral Blood Mononuclear Cells), Splenocytes, Lymph node cells, Plasma, Serum, Spinal fluid
    • Adaptable to your needs, in close collaboration with the CPV and TaRGeT UMR 1089 Gene therapy laboratory research teams

    Gene Therapy Immunology Core – GTI

    Analyses for monitoring the immune response against the vector or the transgene product are carried out by the GTI (Gene Therapy Immunology Core) platform of TaRGeT UMR 1089 Gene therapy laboratory. This platform has complete technical means for the Immune monitoring  of gene therapy studies.

    In a nutshell
    ELISpotCell proliferation testTetramerflow cytometry Cellular neutralization testELISAWestern Blot Luminex Plate washerMultimode microplate reader ELISpot readerTurbo gel transfer system
    • ELISpot
    • Cell proliferation test
    • Tetramer
    • Multi-parametric phenotyping by flow cytometry (in collaboration with the Cytocell platform)
    • Cellular neutralization test
    • ELISA
    • Western Blot (WB)
    • Quantification of cytokines by Luminex
    • Plate washer
    • Multimode microplate reader (Spectrophotometry, Fluorescence, Luminescence)
    • ELISpot reader
    • Turbo gel transfer system

    Preclinical analysis

    Evaluation of the biodistribution and expression profile of transgenes is necessary to understand the pharmacology and pharmacokinetics of a therapeutic product. We are recognized as experts in the molecular and biochemical analyses required to assess the efficacy and biosafety of gene therapy products.

    In a nutshell
    Evaluation of functionality Evaluation of biodistribution Expression Profile Assessmentdevelopment of preclinical studiesAbsolute quantification
    • Evaluation of the functionality of therapeutic products
    • Evaluation of biodistribution and dissemination of gene therapy products after administration
    • Expression Profile Assessment:
      • RT-qPCR (relative quantification of the transgenic messenger)
      • Western-Blot or ELISA on tissues or fluids (specific detection of the transgenic protein)
    • Absolute quantification of the transgenic genome: qPCR on tissues and biological fluids
    • Global coordination and expertise for the development of preclinical studies to evaluate a therapeutic product

    Preclinical analysis core – PAC

    Our leading expertise, in the evaluation of biodistribution and expression profiles of transgenes, is implemented using multiple tools and equipment available on PAC (Preclinical Analytics Core) platform of the Nantes UMR1089 gene therapy laboratory.

    In a nutshell
    Tissue shredderPipetting machineNanophotometermicroplate reader Colorimetric and fluorimetric reader Electrochemiluminescence reader PCR and qPCR instrumentsTurbo gel transfer system
    • Tissue shredder (Qiagen, Tissue Lyser II)
    • Pipetting machine (Hamilton, Microlab Star)
    • Nanophotometer and microplate reader (Thermo Scientific, Multiskan FC)
    • Colorimetric and fluorimetric reader (Tecan, Spark microplate reader)
    • Electrochemiluminescence reader (MSD, quickplex reader)
    • PCR and qPCR instruments (96 and 384 wells, Applied Biosystems, Biorad)
    • Turbo gel transfer system (Trans-blot turbo system, Biorad)

    Engineering at CAPACITÉS

    Our gene therapy experts carry out their engineering work directly in the research laboratories of Nantes Université, particularly in TaRGeT UMR 1089 Gene therapy laboratory
    On a daily basis, they combine technical resources and scientific discoveries to meet your R&D challenges.

    Need an innovative and resourceful partner?

    Capacités teams inspire, harness and couple numerous cutting-edge skills covering a wide range of applications and expertise to meet all of your innovation needs with passion and commitment!

    +33 (0)2 72 64 88 94

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