Non-coding oligonucleotides as broad-spectrum antiviral treatment

The long-term goal is to develop a treatment with broad antiviral effectiveness. We will here focus on a clinically highly relevant pandemic infection: respiratory syncytium virus (RSV). The disease state caused by infections results from viral virulence and/or immunopathology.

Therefore, the most effective approach to manage infectious diseases is to combine inhibition of microbial invasion and preventing inappropriate immune responses.

We have identified non-coding single-stranded oligonucleotides (ssON), which exhibit potent antiviral and immune modulatory activities both in vitro and in vivo in a RSV challenge model.During the next four years, we will in parallel with preclinical development of ssON, elucidate early in vivo events occurring in RSV infected mice by using spatial transcriptomics and in situ hybridization techniques as well as histology and flow cytometry.

We will delineate the innate signaling pathways pivotal for the therapeutic effects by using knock-out mice.

Further, we will monitor the polarizing cytokines and adaptive immune responses including memory after RSV infection with or without treatment with ssON.

Using our combined expertise, we will provide further understanding of events taking place in vivo after RSV infection locally in the lungs and gain new knowledge about immune responses generated and their spatial organization. The expected results will provide a strong background for further clinical development of ssON.