Plant srna extract for use as an immunosuppressive agent

Abstract

The present invention relates to a plant sRNA extract for use as an immunosuppressive agent.

1 - 26 . (canceled) 
     
     
         27 . A method of treating or preventing an inflammatory disease, comprising administering to a patient in need thereof a pharmaceutically effective amount of plant sRNA extract or a composition comprising 2 or more plant sRNA extracts. 
     
     
         28 . A method of preventing an inflammatory disease, comprising administering to a human a plant sRNA extract or a composition comprising 2 or more plant sRNA extracts, wherein said human is a healthy person, or a person not suffering from said inflammatory disease. 
     
     
         29 . The method of  claim 27 , wherein the sRNA in said sRNA extract has a length of 200 nucleotides or less, a length of 120 nucleotides or less, or a length of between 10 and 120 nucleotides. 
     
     
         30 . The method of  claim 27 , wherein the sRNA in said sRNA extract has a length of between 10 and 70, 10 and 60, 15 and 60, 20 and 60, or between 10 and 50 nucleotides. 
     
     
         31 . The method of  claim 27 ,
 wherein the sRNA in said sRNA extract:   (a1) is miRNA, or   (b1) has a length of between 10 and 25 nucleotides or between 10 and 24 nucleotides, or   (c1) is methylated at the 2′OH group of the 3′ terminus, or   said sRNA extract:   (a2) essentially consists of the sRNA of a plant which has a length of 200 nucleotides or less, or   (b2) essentially consists of the sRNA of a plant which has a length of length of between 10 and 120 nucleotides, or   (c2) comprises the sRNA of a plant which has a length of between 10 and 25 nucleotides or between 10 and 24 nucleotides, or   (d2) does not contain ribosomal RNA, or   (e2) is a plant miRNA extract, or   (f2) comprises plant sRNA or plant miRNA methylated at the 2′OH group of the 3′ terminus.   
     
     
         32 . The method of  claim 27 , wherein said plant sRNA extract is selected from an apple sRNA extract, a blueberry sRNA extract, a raspberry sRNA extract, a cabbage sRNA extract, an  Arabidopsis thaliana  sRNA extract, a grape sRNA extract, a rice sRNA extract, a wild rice sRNA extract, a corn sRNA extract, a pine sRNA extract, a fern sRNA extract, a strawberry sRNA extract, a sage sRNA extract, and a strawberry sRNA extract. 
     
     
         33 . A composition comprising or consisting of 2 or more plant sRNA extracts. 
     
     
         34 . The composition of  claim 33 , wherein
 (a) said composition comprises or consists of 2 or more plant sRNA extracts selected from an apple sRNA extract, a blueberry sRNA extract, a raspberry sRNA extract, a cabbage sRNA extract, an  Arabidopsis thaliana  sRNA extract, a grape sRNA extract, a rice sRNA extract, a strawberry sRNA extract, and a fern sRNA extract, or   (b) said composition comprises or consists of, cabbage leaves sRNA extract, fern leaves sRNA extract and apple skin sRNA extract, and optionally strawberry fruit sRNA extract.   
     
     
         35 . The method of  claim 27 , wherein said inflammatory disease
 (a) is selected from the group consisting of chronic prostatitis, Glomerulonephritis, Hypersensitivities, Pelvic inflammatory disease, Reperfusion injury, Sarcoidosis, Vasculitis, Interstitial cystitis, normocomplementemic urticarial vasculitis, pericarditis, myositis, anti-synthetase syndrome, scleritis, macrophage activation syndrome, Bechet's Syndrome, PAPA Syndrome, Blau's Syndrome, gout, adult and juvenile Still's inflammatory disease, cryropyrinopathy, Muckle-Wells syndrome, familial cold-induced auto-inflammatory syndrome, neonatal onset multisystemic inflammatory disease, familial Mediterranean fever, chronic infantile neurologic, cutaneous and articular syndrome, systemic juvenile idiopathic arthritis, Hyper IgD syndrome, Schnitzler's syndrome, TNF receptor-associated periodic syndrome (TRAPSP), gingivitis, periodontitis, hepatitis, cirrhosis, pancreatitis, myocarditis, vasculitis, gastritis, gout, gouty arthritis, and inflammatory skin disorders, selected from the group consisting of psoriasis, atopic dermatitis, eczema, rosacea, urticaria, and acne, or   (b) is an autoimmune disease or an allergic disease.   
     
     
         36 . The method of  claim 35 , wherein
 (a) said autoimmune disease is selected from the group consisting of multiple sclerosis, rheumatoid arthritis; psoriatic arthritis, discoid lupus erythematosus, systemic lupus erythematosus (SLE); ulcerative colitis; Crohn's disease; benign lymphocytic angiitis, autoimmune lymphoproliferative syndrome, sarcoidosis, autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, pure red cell aplasia, Sjogren's syndrome, rheumatic disease, polymyalgia rheumatica, mixed connective tissue disease, inflammatory rheumatism, degenerative rheumatism, extra-articular rheumatism, juvenile arthritis, juvenile rheumatoid arthritis, systemic juvenile idiopathic arthritis, arthritis uratica, muscular rheumatism, chronic polyarthritis, reactive arthritis, Reiter's syndrome, rheumatic fever, relapsing polychondritis, Raynaud's phenomenon, vasculitis, cryoglobulinemic vasculitis, ANCA-associated vasculitis, temporal arteritis, giant cell arteritis, Takayasu arteritis, Behcet's disease, antiphospholipid syndrome, myasthenia gravis, autoimmune haemolytic anaemia, Guillain-Barre syndrome, chronic immune polyneuropathy, chronic inflammatory demyelinating polyneuropathy, autoimmune thyroiditis, insulin dependent diabetes mellitus, type I diabetes, Addison's disease, membranous glomerulonephropathy, polyglandular autoimmune syndromes, Goodpasture's disease, autoimmune gastritis, autoimmune atrophic gastritis, pernicious anaemia, pemphigus, pemphigus vulgaris, cirrhosis, primary biliary cirrhosis, idiopathic pulmonary fibrosis, myositis, dermatomyositis, juvenile dermatomyositis, polymyositis, fibromyositis, myogelosis, celiac disease, celiac sprue dermatitis, immunoglobulin A nephropathy, Henoch-Schonlein purpura, Evans syndrome, atopic dermatitis, psoriasis, psoriasis vulgaris, psoriasis arthropathica, Graves' disease, Graves' ophthalmopathy, scleroderma, systemic scleroderma, progressive systemic scleroderma, diffuse scleroderma, localized scleroderma, Crest syndrome, asthma, allergic asthma, allergy, primary biliary cirrhosis, Hashimoto's thyroiditis, fibromyalgia, chronic fatigue and immune dysfunction syndrome (CFIDS), primary myxedema, sympathetic ophthalmia, autoimmune inner ear disease, autoimmune uveitis, autoimmune chronic active hepatitis, collagen diseases, ankylosing spondylitis, periarthritis humeroscapularis, panarteritis nodosa, polyarteritis nodosa, chondrocalcinosis, Wegener's granulomatosis, microscopic polyangiitis, chronic urticaria, bullous skin disorders, pemphigoid, bullous pemphigoid, cicatricial pemphigoid, vitiligo, atopic eczema, eczema, chronic urticaria, autoimmune urticaria, normocomplementemic urticarial vasculitis, hypocomplementemic urticarial vasculitis, alopecia areata, alopecia universalis, alopecia totalis, Devic's disease, pernicious anemia, childhood autoimmune hemolytic anemia, idiopathic autoimmune hemolytic anemia, refractory or chronic Autoimmune Cytopenias, Prevention of development of Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A, Cold agglutinin disease, Neuromyelitis Optica, Stiff Person Syndrome, gingivitis, periodontitis, pancreatitis, myocarditis, gastritis, gout, gouty arthritis, idiopathic pericarditis, anti-synthetase syndrome, scleritis, macrophage activation syndrome, PAPA Syndrome, Blau's Syndrome, adult and juvenile Still's disease, cryopyrin associated periodic syndrome, Muckle-Wells syndrome, familial cold auto-inflammatory syndrome, neonatal onset multisystem inflammatory disease, chronic infantile neurologic cutaneous and articular syndrome, familial Mediterranean fever, Hyper IgD syndrome, Schnitzler's syndrome, autoimmune retinopathy, age-related macular degeneration, and TNF receptor-associated periodic syndrome (TRAPS), or   (b) said allergic disease is selected from the group consisting of allergic respiratory disease, such as bronchial asthma, pediatric asthma, allergic asthma, atopic asthma, aspirin asthma, or allergic bronchitis, allergic nasal disease, such as allergic rhinitis, vernal catarrh, hay fever, or chronic allergic rhinitis, an allergic skin disease, such as atopic dermatitis, an allergic ocular disease, such as hay fever, seasonal allergic conjunctivitis, or chronic allergic conjunctivitis, hypersensitivity pneumonitis, contact dermatitis, and food allergy, or   (c) said inflammatory disease is psoriasis.   
     
     
         37 . The method of  claim 27 , wherein said inflammatory disease is characterized by an increase in expression or production of at least one of inflammatory biomarker selected from IL-1β and TNFα or wherein said inflammatory disease is characterized by a dysregulation of the cytokines or co-receptors in at least one cell or tissue of a patient, wherein the at least one cell is a dendritic cell. 
     
     
         38 . The method of  claim 27 , wherein said sRNA extract is derived from strawberry, or wherein said composition comprises a strawberry sRNA extract. 
     
     
         39 . The method of  claim 27 , wherein said plant sRNA extract or said composition is administered in combination with at least one other anti-inflammatory agent. 
     
     
         40 . The method of  claim 39 , wherein said other anti-inflammatory agent is selected from the group consisting of a corticosteroid, a statin, interferon beta, a nonsteroidal anti-inflammatory drug (NSAID), methotrexate, Cyclosporin A and a disease-modifying anti-rheumatic drug (DMARD). 
     
     
         41 . The method of  claim 27 , wherein said plant sRNA extract or said composition is comprised in a food additive or dietary supplement. 
     
     
         42 . The method of  claim 27 , wherein said plant sRNA extract or said composition is comprised in a pharmaceutical composition. 
     
     
         43 . A pharmaceutical composition, food product, food additive or dietary supplement, comprising a composition comprising 2 or more plant sRNA extracts, or a plant sRNA extract, optionally wherein the pharmaceutical composition, food product, food additive or dietary supplement comprises a) lipids, or b) an exosome. 
     
     
         44 . The pharmaceutical composition, food product, food additive or dietary supplement of  claim 43 , wherein
 the sRNA in said sRNA extract:   (a1) is miRNA, or   (b1) has a length of between 10 and 25 nucleotides or between 10 and 24 nucleotides, or   (c1) is methylated at the 2′OH group of the 3′ terminus, or   said sRNA extract:   (a2) essentially consists of the sRNA of a plant which has a length of 200 nucleotides or less, or   (b2) essentially consists of the sRNA of a plant which has a length of length of between 10 and 120 nucleotides, or   (c2) comprises the sRNA of a plant which has a length of between 10 and 25 nucleotides or between 10 and 24 nucleotides, or   (d2) does not contain ribosomal RNA, or   (e2) is a plant miRNA extract, or   (f2) comprises plant sRNA or plant miRNA methylated at the 2′OH group of the 3′ terminus, or   (g2) is selected from an apple sRNA extract, a blueberry sRNA extract, a raspberry sRNA extract, a cabbage sRNA extract, an  Arabidopsis thaliana  sRNA extract, a grape sRNA extract, a rice sRNA extract, a corn sRNA extract, a pine sRNA extract, a fern sRNA extract a sage sRNA extract, and a strawberry sRNA extract.   
     
     
         45 . A method for producing a second food product, comprising adding to a first food product a plant sRNA extract, or a composition comprising 2 or more plant sRNA extracts.