Structure and use of 5'phosphate oligonucleotides

Abstract

Oligonucleotides bearing free, uncapped 5′ phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1β production. Bacterial RNA also induces type I IFN production. 5′ phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1β production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5′ triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1β production, in a target cell-specific manner.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the field of immunotherapy and drug discovery. The present invention provides oligonucleotides which are capable of inducing an anti-viral or an anti-bacterial response, in particular, the production of type I IFN, IL-18 and / or IL-1β, and their in vitro as well as therapeutic uses.BACKGROUND OF THE INVENTION[0002]The vertebrate immune system established different ways to detect invading pathogens based on certain characteristics of their microbial nucleic acids. Detection of microbial nucleic acids alerts the immune system to mount the appropriate type of immune response that is required for the defense against the respective type of pathogen detected. Detection of viral nucleic acids leads to the production of type I interferon (IFN) including IFN-α and IFN-β, the key cytokines for anti-viral defense.[0003]IFN-α was the first type of interferon to be identified and commercialized; it is widely used clinically in the treat...

AI Technical Summary

Problems solved by technology

IFN-α products that are currently in clinical use include the recombinant protein and the highly purified natural protein, both of which have high production costs.

Furthermore, IFN-α is currently administrated systematically and causes a broad spectrum of side effects (e.g. fatigue, flu-like symptoms, diarrhea).

Most alarmingly, IFN-α causes a decrease in bone marrow function which leads to increased susceptibility to life-threatening infections, anemia and bleeding problems.

In the cytoplasm, abundant self RNA complicates our understanding of the recognition of

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