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From Proof of Concept to CDMO

TcBuster graphic

At Bio-Techne, we have developed innovative editing technologies for genome engineering, and we leverage them with our vast cell culture experience. Our gene engineering services team specializes in complex projects and hard-to-transfect cell lines. We come through where others before us have failed. Let us solve your difficult and challenging gene engineering projects so you can focus on groundbreaking research and manufacturing!

What can we do for you?

  • Modify your cells using TcBuster, a non-viral gene delivery system
  • Custom gene editing services to deliver simple and complex engineering solutions in a realistic timeframe
  • iPSC engineering services (RUO and GMP capabilities) for stem cell and regenerative medicine therapies
  • GMP Process Development (PD) for your CAR-T, TCR, or iPSC therapies
  • Other contract development and manufacturing organization (CDMO) services

Why Do You Want To Use Our Genome Engineering Services?

Gene Engineering in Basic Research

 

  • Alteration of cell phenotype - gene knock-in (KI) or knock-out (KO) to investigate changes in cell phenotype.
  • In vivo cellular function – cellular modification to study its behavior in the overall animal.
  • Protein localization – introduction of tags into a protein for monitoring intracellular protein trafficking.
  • Targeted protein degradation (TPD) - tagging a protein to understand and study protein functionality.
  • Immunoassay development – validation of antibody specificity and assay performance.
  • Protein-protein interactions – defining molecular interactions in complex pathways.

Gene Engineering in Therapeutics Development

 

  • Disease models – development of animal models carrying molecular variants associated with human diseases.
  • Drug discovery - alteration of genes which encode proteins that serve as drug targets. Genetic screens speed the identification of novel drug candidates and improve drug efficacy and specificity.
  • Gene therapy – delivery of genes into relevant cell types to correct genetic defects.
  • Cancer immunotherapies – engineering cells to express designer proteins that specifically target tumor cells, e.g. CAR-T cells.
  • Diagnostic tools – engineering cells to express proteins for detection of infectious and non-infectious diseases.
  • Vaccine development – stable overexpression of immunodominant viral proteins to elicit protective immunity.

We come through where others before us have failed. Let us solve your difficult and challenging gene engineering projects so you can focus on groundbreaking research and manufacturing!

Overview of TcBuster Transposition Mechanism

 

TcBuster is a next-generation, non-viral gene delivery system that enables stable transfer of a gene of interest (GOI) into any cell type. It is based on a DNA transposon from the red flour beetle and has the potential to deliver therapeutic genetic payloads to address a broad range of therapeutic applications. The adoption of TcBuster in cell and gene-modified cell therapy processes can replace the use of retroviral and lentiviral vectors, leading to significant time savings during the development of cell therapeutics.

Genome Engineering in the Immunotherapy Workflow

Genome engineering is a mid-process step in cell therapy manufacturing. It takes place following isolation and activation of the desired immune cell population (e.g. T cells or NK cells). In gene editing, the cell’s genome is altered to generate a functional therapeutic cell population that will attack the patient’s disease. This may involve introduction of a disease-targeting chimeric antigen receptor (CAR) or TCR, inactivation of negative regulatory molecules, or alterations to enable the cells to avoid host immunity. Following genome engineering, the cells are expanded ex vivo, characterized, and infused into the patient.

Genome Engineering in the Targeted Protein Degradation Workflow

Genome Engineering is an essential component of the TAG Degradation Platform for target validation. Cells are engineered to express a protein of interest as a fusion with a TAG domain. A bifunctional small molecule TAG Degrader (dTAG or aTAG) that concomitantly binds the TAG domain and an E3 ligase, recruits the fusion protein for ubiquitination, which targets it for destruction by the proteasome. This enables exploration of the downstream consequences of target protein knockdown in cells. Learn more in our whitepaper Validating Targets for Targeted Protein Degradation using dTAG.

Comparison of Non-Viral and Virus-Based Systems

Viral approaches (e.g. with lentivirus or AAV) involve transduction of the target cells, while non-viral transposons are electroporated into the target cells. Transposons have demonstrated a safe insertion profile without preference for any specific genomic sites. They maintain high efficiency gene transfer and stable expression, enabling rapid generation of transgenic mammalian cells with limited off-target effects.

TcBuster is the only commercially available transposon system, which means that its use is not limited by licensing restrictions. Bio-Techne’s genome engineering services with TcBuster address cell manufacturing process challenges by:

  • Reducing the costs of genetic modification
  • Providing cells engineered with GMP manufacturing controls in 4 months
  • Improving the ability to integrate larger cargo sizes than practical with viral based methods
  • Providing flexibility to utilize TcBuster with additional gene editing techniques in one operation

TcBuster shortens timelines and reduces the risk of delays. It is a valuable tool for both proof-of-concept studies and manufacturing scale process development.

TcBuster Gene Transfer Total Time: 8-14 Weeks

TcBuster Mechanism graphic

Viral-Based Gene Transfer Total Time: 11-20 Weeks

Cell Engineering Services

Cell Engineering Services graphic

No cell line is too difficult for us to engineer, and our highly efficient genome editing process speeds up delivery timelines. We offer dedicated project management supported by our Custom Services team. Regardless of the project, we can customize all deliverables including the number of cells/vial, validation testing, datasheet preparation, and batch record documentation. We will work with you to make sure we engineer the right solution for your needs!

  • RUO and GMP capabilities
  • Multiplex gene knock-out and knock-in
  • Conditional knock-out system
  • Correction or introduction of single nucleotide polymorphisms (SNPs)
  • Banking of wild-type clones and backup storage of engineered cells

Cell Line Engineering and Primary Cell Processing

Let Us Handle These Steps For You

  • Consultation and preparation – speak with our gene editing experts who work with you to provide a solution that works for you.
  • Isolation of your desired primary cells at small or large scale. We can obtain nearly any cell type  (e.g. CD34+ cells, T cells, B cells, MSCs) including specific donor characteristics (e.g. HLA type, sex, CMV status).
  • Gene engineering/editing with any platform to generate high frequency gene knock-outs, knock-ins, or multiplex edits.
  • Cell selection and expansion to maintain high functionality and viability (typically >95%).
  • Validation of engineered cells – genetic (PCR), protein expression (Western blot or flow cytometry), and custom functional analysis.
  • Cryopreservation with customized number of cells/vial and number of vials.

iPSC Engineering Services

iPSC Engineering Image

Induced pluripotent stem cells (iPSCs) are an invaluable source in regenerative medicine due to their ability to differentiate into a variety of cell lineages. They are produced by the reprogramming of differentiated somatic cells such as PBMCs, fibroblasts, and patient-specific samples. Unlike endogenous PSCs, iPSCs are not derived from human embryos, and they avoid bioethical obstacles arising from the use of embryo-derived stem cells.

Genomic engineering of iPSCs can fine tune their function and performance in regenerative medicine therapies. They can be engineered to address genetic defects, promote the rebuilding of damaged tissues, and avoid immune rejection after implantation. iPSCs hold great promise for the treatment of many overwhelming and life-threatening diseases that are currently incurable.

Challenges in iPSC Engineering

  • Licensing complexities (e.g. consent and licensing from donors, licensing of gene integration methods). iPSC lines generated with non-integrating methods may not be approved for clinical use due to intellectual property restrictions.
  • Extended timeline resulting from complexities and time requirements for optimization of iPSC generation

Our iPSC Processing Services for RUO, GMP, and Xeno-free Environments

  • iPSC reprogramming, expansion, and master cell banking
  • Gene knock-out
  • Gene knock-in
  • Multiplex gene editing (simultaneous knock-out/knock-in)
  • Insertion or correction of single nucleotide polymorphisms (SNPs)
  • HLA engineering to increase immunological compatibility with patient

Benefits of Our iPSC Cell Processing Services

  • All services from gene editing to differentiation performed in-house
  • Our cell culture experts have experience working under feeder, feeder-free, and xeno-free culture conditions
  • We have a flexible platform to successfully edit cells from healthy or diseased donors
  • We provide customizable validation assays and documentation
  • Our dedicated project management team provides timely updates to inform progress of projects

GMP Cell Processing and Engineering Services

Cell Processing Cleanrooms at Bio-Techne

Our mission is to deliver innovative solutions that enable cell and gene therapies to reach more patients. Our commitment as your partner extends beyond an optimal process for your therapy. From the outset we work with you to build in the flexibility needed to meet the demands of scaling to commercialization.

As a contract development and manufacturing organization (CDMO), we offer in-house process development for gene modified therapies, GMP patient sample processing for Phase I and Phase II clinical trials, and GMP manufacturing of iPSC cell lines.

If you are ready for the next steps, set up a free consultation today.

Process Development

During PD, we will optimize your program into a reliable process that’s robust enough for clinical manufacturing at scale.

  • Selection of raw materials with supply agreements
  • In-house testing along with testing in your hands as appropriate
  • GMP manufacturing suite scheduling
  • Regular process evaluation and troubleshooting

GMP Manufacturing

When your process is ready for manufacturing, we’ll move into our in-house clean room suites for engineering runs and producing your clinical cell or gene therapy. Our facilities are ISO Class 7 certified (Class 10,000) with associated development and quality control labs. Our Quality Team provides regulatory support and oversees facility maintenance, automated batch records, personnel training, and raw materials inspection, testing, and tracing. We will customize your end product according to the QC testing, vialing, and labeling demanded by your process.

Tell us about your project, and one of our experts will contact you to discuss how we can help.