5'-triphosphate Oligonucleotides Having Blunt End and Uses Thereof

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This patent discloses specially designed oligonucleotides (short strands of nucleic acids) that have at least one blunt end, a 5'-triphosphate group, and a sufficiently long double-stranded region. These oligonucleotides are highly effective at activating RIG-I, a cellular sensor responsible for triggering strong antiviral immune responses, particularly by inducing type I interferon (IFN) production. Furthermore, these oligonucleotides can be engineered with gene-silencing properties (as siRNAs), allowing them to both silence specific disease-related genes and simultaneously stimulate innate immunity. The invention is relevant for treating a wide array of diseases, especially viral infections, cancer, and immune disorders.

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• Therapeutic agents for treating viral infections (e.g., influenza, RSV, hepatitis B and C, Ebola, rabies, etc.) by enhancing the body's antiviral response via RIG-I activation.
• Cancer (especially melanoma and other solid tumors) therapy by combining direct tumor cell apoptosis (via gene silencing, e.g., Bcl-2) and immune stimulation, leading to tumor regression.
• Use as vaccine adjuvants to boost innate and adaptive immune responses for better vaccine efficacy.
• Research tools for studying immune pathways, IFN biology, or gene function in vitro and in vivo.
• Treatment for certain immune disorders by modulating the type I IFN response.
• Potential application in controlling overactive immune responses (autoimmunity or virus-induced cytokine storms) by selective design of oligonucleotides to antagonize IFN pathways.

BenefitsContent extracted from patent full text and abstract with AI.

• Ability to induce strong antiviral IFN responses via specific RIG-I activation, offering potent host defense mechanisms.
• Dual functionality: gene-silencing (RNA interference) and immune activation within the same molecule, enhancing therapeutic impact.
• Targeted action: can be directed against specific disease genes (e.g., Bcl-2 oncogene in cancer cells), increasing efficacy and limiting off-target effects.
• Synthetic, chemically defined oligonucleotides allow for precise manufacturing, purity control, and specific modifications for stability or enhanced activity.
• Versatility: applicable to a wide range of diseases, including viral infections, various cancers, immune disorders, and as a research/reagent tool.
• Tunability: the immunostimulatory activity can be further enhanced or suppressed via chemical modifications, allowing fine control for different clinical needs.

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Patent Abstract

PROBLEM TO BE SOLVED: To provide oligonucleotides capable of activating RIG-I, and eliciting anti-viral responses, particularly IFN response in cells expressing RIG-I, as well as oligonucleotides capable of activating RIG-I and suppressing a target gene.SOLUTION: Provided is an oligonucleotide having at least one blunt end comprising a double-stranded portion of at least 19 bps, preferably at least 21 bps, at least one 5' triphosphate and at least one blunt end which bears a 5'-triphosphate. The oligonucleotide is used to elicit anti-viral response, particularly, IFN response in vitro and in vivo, as well as to prevent and/or treat diseases or conditions such as infections, tumors/cancers and immune disorders.