Extracellular vesicle mimetics as delivery vehicles for oligonucleotide-based therapeutics and plasmid DNA

细胞外囊泡模拟物作为寡核苷酸治疗药物和质粒 DNA 的运载载体

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作者:Anastasiya Oshchepkova, Ivan Chernikov, Svetlana Miroshnichenko, Olga Patutina, Oleg Markov, Innokenty Savin, Yaroslav Staroseletz, Mariya Meschaninova, Pavel Puchkov, Sergey Zhukov, Maxim Kupryushkin, Mikhail Maslov, Aleksandra Sen'kova, Valentin Vlassov, Elena Chernolovskaya, Marina Zenkova

Discussion

CINVs demonstrated unique properties for the delivery of therapeutic nucleic acids, especially for antisense oligonucleotide-based therapy.

Methods

Here we used EV mimetics produced by cell treatment with the actin-destabilizing agent cytochalasin B as an alternative to EVs for the delivery of therapeutic nucleic acids.

Results

Cytochalasin-B-inducible nanovesicles (CINVs) delivered a fully modified N-(methanesulfonyl)- or mesyl (µ-) antisense oligonucleotide to B16 melanoma cells, selectively decreasing the level of target microRNA-21 with effectiveness comparable to that observed upon Lipofectamine 2000-mediated delivery. The efficiency of the CINV-mediated delivery of plasmid DNA encoding EGFP varied depending on the type of recipient cells. Surprisingly, under experimental conditions, CINVs were unable to deliver both modified and natural short RNA duplexes-small interfering RNA and immunostimulatory RNA-probably due to their poor loading into CINVs.

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