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IcoCell Technology

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IcoCell Technology

IcoCell is a proprietary cell line development platform to efficiently generate CHO-based stable high-performance cell lines. These serve for large-scale GMP production of therapeutic recombinant proteins and monoclonal antibodies, both for clinical trial materials as well as for industrial-scale commercial production afterwards.

The IcoCell platform is based on a proprietary, fully biosafety-tested CHO-S starter cell line, which is stably modified with a regulatory approved viral transcriptional enhancer. This IcoCell modification ensures the transgenes’ semi-directed and stable integration into transcriptionally active open chromatin, yielding controlled, strong, and lasting protein expression levels.

IcoCell Technology

IcoCell Cell Line Development Platform



The IcoCell transcription-enhancing factor, together with cognate transcriptional DNA elements, engineered into any stable IcoCell cell line, ensures a strong and stable expression of the transgene. Also, this factor prevents transgene silencing during clone selection and later large-scale GMP production.



The IcoCell cell line development path follows a rigorous analytical regimen with ever-increasing stringency on the product. cellular and manufacturability level.



Full documentation in form of a complete cell line development report is provided, which is essential for later regulatory submission and GMP manufacturing.



The VIPS™ Verified In-Situ Plate Seeding method allows one quick single cell cloning round, yet assuring 99.9% monoclonality.



Our stable high producer clone pool approach yields grams-per-liter titers already weeks after CLD starts. These clone pools, together with our in-house DSP and analytical capabilities enable rapid assessment of early recombinant protein, e.g. in early in vivo studies. Analytical and formulation development as well as product stability studies can be started ahead of time.



Any recombinant IcoCell CHO cell line is routinely tested to confirm being stable over at least 60 population doublings. This ensures constant product quality and yield from vial-cracking to several thousand-liter manufacturing scale.

From Antibody Discovery to Stable CHO Cell Line Development and in-house GMP Manufacturing:

One Site. One Team. One Project. Saving Time, Costs, and Nerves. 

VIPS™ Double Lock Monoclonality Assurance

Icosagen’s automated single-cell cloning cell line development workflow combines gentle single-cell printing with in-well droplet and whole-cell imaging. The VIPS™ System ensures that every production cell line is a true mono-clone derived from one single progenitor cell. The VIPS™ (Verified In situ Plate Seeding) automatically captures and documents the journey from a single cell to colony outgrowth into a comprehensive clonality report. High-clarity images and accompanying data provide a unique ‘double lock’ of clonality assurance of 99.9% for IND submission. 

Additional safety method to the automation-based VIPS™-based clonality report, a further routine visual inspection of the images by experienced CLD scientists assures that every cell line was indeed derived from one single cell. 

Step 1. Single-cell seeding evidence

Cells are imaged in multiple z-stack layers in the dry empty well before intelligence-based image analysis confirms the existence of a single cell. 
The well is then carefully filled with medium.

Step 2. Clonal growth phase

During the clonal growth phase, VIPS™ performs daily high-clarity whole-well imaging, recording a timeline of well images and at the same time, performing confluency analysis. Successful clonal outgrowth can so be traced back to a single cell to confirm monoclonality.
This picture illustrates how Icosagen uses Solentim VIPS Single Cell Cloning Instrument in single cell cloning, using two step assurance, also called as "double lock" method.

Science Behind IcoCell Technology

The IcoCell technology is a proprietary platform to develop biopharmaceutical high-producer clones in CHO cells, with competitive titers and timelines, and robust, predictive large-scale manufacturing properties for therapeutic proteins and antibodies.

We have designed and optimized the entire Icosagen workflow and IcoCell technology platform such that our clients’ product candidates transition seamlessly and rapidly from the discovery and lead candidates’ stage into a clinical development path, ending with GMP-produced clinical trials drug substance.

IcoCell CHO Cell Line Development and Biosafety Testing
The “empty” CHO IcoCell is genetically stably modified with the regulatory accepted IcoCell transcriptional activator molecule, and afterwards passed a rigorous MCB biosafety testing procedure, as conducted for any completed MCB (Master Cell Bank).

Optimized Gene Expression in IcoCell CHO Cell Lines for Maximal Yield and Quality
For every new-to-be-created IcoCell CHO cell line, the entire gene for the encoded mAb/protein of interest is first optimized for maximal yield and product quality. During IcoCell cell line development, the transgene’s DNA from the the proprietary IcoCell-corresponding expression vector is transfected into the empty starter cell. The IcoCell transcriptional activator mediates the optimal, semi-directed integration of the transgene sequences into the active open chromatin in the CHO chromosomes. 

The Role of IcoCell Transcriptional Activator – Integration and Prevention of Transgene Silencing
The robust, regulatory accepted IcoCell transcriptional activator fulfills two tasks at once. First, in a concerted action with corresponding activator binding sites on the IcoCell expression vector, it facilitates the semi-directed integration of the transgene expression cassette into transcriptionally active regions of the CHO host cells’ chromatin, thereby ensuring the controlled and strong expression of the recombinant antibody/protein product. Secondly, the IcoCell transcriptional activator prevents the transgenes’ transcriptional silencing during clonal cell line development and later industrial-scale commercial GMP manufacturing. This way the proprietary IcoCell technology also guarantees the long-lasting expression of the protein of interest over many population doublings, even in commercial thousands of liters bioreactor scales. 

Upstream and Downstream Process Optimization For Product Quality and Yield
During upstream and downstream process development, the protein production conditions are further optimized for yield and quality, yet with a close eye on the economic and regulatory aspects of all process steps developed and materials & consumables employed.
Optimization parameters include  e. g. high viable cell densities, cell growth rates, high-performance metabolic parameters, bioreactor occupation times, as well as impurities-removement, product retainment, etc., all specific to the relevant protein of interest for continuous and optimal product quality and yields. 

This picture illustrates Icosagen’s proprietary IcoCell technology platform for cell line development. The DNA expression vector contains unique, built-in DNA cis- elements, responding to the IcoCell® expression-enhancing factor.

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