Vitamin B12 as a delivery vehicle for antibacterial oligonucleotide analogues

The widespread emergence of bacterial resistance to existing antibiotics creates a need to develop other therapeutic agents. The use of short, modified oligonucleotides as inhibitors of bacterial translation seems a promising strategy. Such specifically designed oligonucleotides suppress proper expression of bacterial genes by complementary binding to bacterial DNA or RNA. However, the main and yet unsolved problem precluding their use is that bacteria do NOT uptake oligonucleotides from their environment. Therefore, the main objective of this proposal is to find an efficient and a non-invasive way for the delivery of short oligonucleotides to prokaryotic cells. We envisage that conjugation of RNA analogues to vitamin B12 will significantly improve their cellular uptake in bacteria. Therefore, in this project we have been synthesizing vitamin B12-oligomer conjugates and evaluating their uptake by bacterial cells.

Principal Investigator of the Symfonia project: Prof. Dorota Gryko, IChO PAN  

PI from the CeNT UW side: dr hab. Joanna Trylska, CeNT UW  

Project period: 2014 – 2019