Supramolecular bioconjugation strategy for antibody-targeted delivery of siRNA

Manon Ripoll (1) , Héloïse Cahuzac (1) , Igor Dovgan (1) , Sylvain Ursuegui (1) , Patrick Neuberg (1) , Stephane Erb (2, 3) , Sarah Cianférani (2, 3) , Antoine Kichler (4) , Jean-Serge Remy (1) , Alain Wagner (1)

1 CBST - Chémo-Biologie Synthétique et Thérapeutique
2 DSA-IPHC - Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires
3 LSMBO - Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg]
4 BB - Biomatériaux et Bioingénierie

RNA interference is a widely used biological process by which double-stranded RNA induces sequence-specific gene silencing by targeting mRNA for degradation. However, the physicochemical properties of siRNAs make their delivery extremely challenging, thus limiting their bioavailability at the target site. In this context, we developed a versatile and selective siRNA delivery system of a trastuzumab-conjugated nanocarrier. These immunoconjugates consist of the assembly by electrostatic interactions of an oligonucleotide-modified antibody with a cationic micelle for the targeted delivery of siRNA in HER2-overexpressing cancer cells. Results show that, when associated with the corresponding siRNA at the appropriate N/P ratio, our supramolecular assembly was able to efficiently induce luciferase and PLK-1 gene silencing in a cell-selective manner in vitro.

Domaines: Chimie

Manon Ripoll, Héloïse Cahuzac, Igor Dovgan, Sylvain Ursuegui, Patrick Neuberg, et al.. Supramolecular bioconjugation strategy for antibody-targeted delivery of siRNA. Bioconjugate Chemistry, 2024, Online ahead of print. ⟨10.1021/acs.bioconjchem.4c00304⟩. ⟨hal-04728199⟩