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OR06

Development of a bio-inspired nanovector for targeted cancer gene therapy.

T Briolay ¹ ² ³ ⁴ ⁵   T Petithomme ¹ ² ³ ⁴ ⁵   J Fresquet ¹ ² ³ ⁴ ⁵   C Blanquart ¹ ² ³ ⁴ ⁵

1: Université de Nantes    2: Inserm UMR 1307    3: CNRS UMR 6075    4: Université d'Angers    5: CRCI2NA

Over the past few decades, the field of nanovectorization has emerged to address the main limitations of current anti-cancer drugs: (i) systemic toxicity due to low tumor selectivity; (ii) low plasma stability; (iii) limited tumor uptake resulting in a poor therapeutic efficacy, and eventually (iv) poor solubility. Synthetic nanoparticles are currently the most represented nanovectors in clinical trials but interest in new protein-based carriers such as virus-like particles (VLPs) is also growing due to their better biocompatibility. VLPs can be derived from animal, plant or bacteria viruses and consist in a non-replicative viral capsid free of viral genome that can be further engineered to target tumor cells. Thanks to their viral origin, VLPs are particularly suited for nucleic acids delivery. In this context, we derived the filamentous bacteriophage M13 to obtain non-replicative VLPs actively targeted to mesothelin, a tumor antigen widely overexpressed in several cancers. These VLPs contain a eukaryotic ORF for transgene expression in human cells. At this point, we showed that these VLPs are selectively internalized by MSLNᵖᵒˢ tumor cells, but not healthy cells, by flow cytometry and in co-culture experiments by confocal microscopy. We also demonstrated that those VLPs can be used to express a reporter transgene in human tumor cells. Moreover, we showed that these VLPs can be easily conjugated to a fluorochrome for an easy tracking in vitro. Following those encouraging results, we will assess VLP biodistribution in tumor models in vivo and evaluate a therapeutic transgene for cancer-specific gene therapy.

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