ONCOTHEIS

Genetically Modified OncoCilAir™

“Applying genetic editing power to Human microtissues”

Genetic editing has proven to be very effective in vivo or in vitro to model pathological conditions and decipher underlying molecular mechanisms.

Here we took advantage of genetic tools (Lentiviruses) to introduce KRAS and TP53 oncogenes into human primary bronchial cells to induce in vitro lung cancer starting from healthy donors.

Similar genetic modification strategies (CRISPR) can be used to model on demand any human respiratory pathological condition relying on genetic alterations (e.g. Cystic Fibrosis).

A genetic in vitro model of lung cancer

Current models suggest that early cancer development involves mutations in genes driving cell proliferation (KRAS) and DNA damage response (TP53). Here we propose a version of OncoCilAir™ microtissue where naïve primary human epithelial bronchial cells have been directly genetically modified to express KRAS or/and TP53 mutants in order to recapitulate the cascade of events leading to lung cancer.

mutants
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Bright field and fluorescence pictures showing the apparition of proliferative clusters inside the mutated 3D tissue, reminiscent of the early lung cancer stages dysplasia and adenoma. A549 adenocarcinoma was used as reference for maximal malignant proliferation in OncoCilAir™.

Mutant growth analysis for anticancer compounds evaluation

Thanks to OncoCilAir™ long lifetime (months), it is possible to follow the growth of different mutant combinations and to test the effect of various anticancer therapies

Relevant Genetic Background

Of note, it is possible to build the model starting from bronchial cells coming from specific donors, like smokers, and thus benefit of relevant genetic and epigenetic background shaped by years of active smoking.

Endpoints

Standard OncoCilAir™ endpoints can be measured throughout the treatment:

In addition, protein and gene expression analyses can be performed by applying state-of-the-art genomics technologies to the tested cultures.


Test GM-OncoCilAir™ microtissues in your facility
Contract us to customize your own airway mutant microtissue and/or to evaluate your compounds

To learn more about GM-OncoCilAir™ services, please contact us