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.

Project Principal Investigators: Prof. Dorota Gryko, IChO PAN and prof. Joanna Trylska, CeNT UW

Project period: 2014 – 2019

Funding: National Science Centre, SYMFONIA