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Vitamin B₁₂ transports modified RNA into E. coli and S. Typhimurium cells

Giedyk, Maciej, Jackowska, Agnieszka, Równicki, Marcin, Kolanowska, Monika, Trylska, Joanna, Gryko, Dorota
Chemical communications 2019 v.55 no.6 pp. 763-766
DNA, Escherichia coli, RNA, Salmonella Typhimurium, alkynes, antibiotics, bacteria, chemical reactions, genes, oligonucleotides, protein synthesis, therapeutics, vitamin B12
Specifically designed, antisense oligonucleotides are promising candidates for antibacterial drugs. They suppress the correct expression of bacterial genes by complementary binding to essential sequences of bacterial DNA or RNA. The main obstacle in fully utilizing their potential as therapeutic agents comes from the fact that bacteria do not uptake oligonucleotides from their environment. Herein, we report that vitamin B₁₂ can transport oligonucleotides into Escherichia coli and Salmonella typhimurium cells. 5′-Aminocobalamin with an alkyne linker and azide-modified oligonucleotides enabled the synthesis of vitamin B₁₂–2′OMeRNA conjugates using an efficient “click” methodology. Inhibition of protein expression in E. coli and S. Typhimurium cells indicates an unprecedented transport of 2′OMeRNA oligomers into bacterial cells via the vitamin B₁₂ delivery pathway.