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 . A plant sRNA extract for use as an immunosuppressive agent. 
     
     
         2 . The plant sRNA extract for use of  claim 1 , wherein the sRNA has a length of 200 nucleotides or less, preferably a length of 120 nucleotides or less, preferably a length between 10 and 120 nucleotides. 
     
     
         3 . The plant sRNA extract for use of  claim 1  or  2 , wherein the sRNA has a length of between 10 and 70, 10 and 60, 15 and 60, 20 and 60, or between 10 and 50 nucleotides. 
     
     
         4 . The plant sRNA extract for use of any of  claims 1 ,  2  or  3 , wherein the sRNA is miRNA. 
     
     
         5 . The plant sRNA extract for use of any of  claims 1  to  4 , wherein the 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, in particular a wild rice sRNA extract, a corn sRNA extract, a pine sRNA extract, a fern sRNA extract and a sage sRNA extract. 
     
     
         6 . The plant sRNA extract for use of any of  claims 1  to  5 , wherein the plant sRNA extract is selected from an apple sRNA extract, cabbage sRNA extract, strawberry sRNA extract and fern sRNA extract,
 preferably wherein 
 the apple sRNA extract is an sRNA extract from apple skin, or 
 the cabbage sRNA extract is an sRNA extract from cabbage leaves or cabbage flower, more preferred from cabbage leaves, or 
 the fern sRNA extract is an sRNA extract from fern leaves, or 
 the strawberry sRNA extract is an sRNA extract from strawberry fruit. 
 
     
     
         7 . A composition comprising 2 or more plant sRNA extracts, preferably wherein the composition comprises 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, in particular a wild rice sRNA extract, a corn sRNA extract, a pine sRNA extract, a fern sRNA extract and a sage sRNA extract,
 more preferably   wherein the composition comprises, preferably consists of two or more sRNA extracts selected from strawberry sRNA extract, namely  Fragaria vesca  sRNA extract, cabbage sRNA extract, fern sRNA extract and apple sRNA extract.   
     
     
         8 . A composition according to  claim 7 , which comprises, preferably consists of, cabbage leaves sRNA extract, fern leaves sRNA extract and apple skin sRNA extract, and optionally strawberry fruit sRNA extract. 
     
     
         9 . The plant sRNA extract for use according to any of  claims 1  to  6 , or the composition of  claim 8 , wherein the sRNA comprises methylated sRNA, more preferably sRNA or miRNA methylated at the 2′OH group of the 3′ terminus. 
     
     
         10 . The composition according to  claim 8  or  9 , for use as an immunosuppressive agent. 
     
     
         11 . A plant sRNA extract, preferably as defined in any of  claims 2  to  6  and  9 , or a composition according to  claim 7 ,  8  or  9 , for use in a method for treating and/or preventing an inflammatory disease,
 in particular wherein the inflammatory disease 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. 
 
     
     
         12 . The plant sRNA extract or composition for use according to  claim 11 , wherein said inflammatory disease is an autoimmune disease. 
     
     
         13 . The plant sRNA extract or composition for use according to  claim 12 , wherein 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),
 preferably wherein said autoimmune disease is multiple sclerosis.   
     
     
         14 . The plant sRNA extract or composition for use according to  claim 11 , wherein said inflammatory disease is an allergic disease. 
     
     
         15 . The plant sRNA extract or composition for use according to  claim 14 , wherein 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. 
     
     
         16 . The plant sRNA extract or composition for use according to  claim 11 , wherein said inflammatory disease is psoriasis. 
     
     
         17 . The plant sRNA extract or composition for use according to any of  claims 11  to  16 , wherein the inflammatory disease is characterized by an increase in expression or production of at least one of inflammatory biomarker, in particular selected from IL-1β and TNFα and/or wherein the inflammatory disease is characterized by a dysregulation of the cytokines or co-receptors in at least one cell and/or tissue of a patient, in particular wherein the at least one cell is a dendritic cell. 
     
     
         18 . The plant sRNA extract for use according to any of  claims 1  to  6 ,  9  or  11  to  17 , wherein said sRNA extract is derived from strawberry, or the composition of any of  claims 7  to  9 , or the composition for use of any of  claims 11  to  17 , wherein said composition comprises a strawberry sRNA extract. 
     
     
         19 . The plant sRNA extract for use according to any of  claims 1  to  6 ,  9  or  11  to  18  or the composition for use of any of  claims 11  to  18 , wherein said plant sRNA extract or composition is administered in combination with at least one other anti-inflammatory agent. 
     
     
         20 . The plant sRNA extract or composition for use according to  claim 19 , 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). 
     
     
         21 . The plant sRNA extract for use according to any of  claims 1  to  6 ,  9  or  11  to  20  or the composition for use of any of  claims 11  to  20 , or the composition of any of  claims 7  to  9 , wherein said plant sRNA extract or composition is comprised in a food additive or dietary supplement. 
     
     
         22 . The plant sRNA extract for use according to any of  claims 1  to  6 ,  9  or  11  to  19  or the composition for use of any of  claims 11  to  19 , wherein said plant sRNA extract is comprised in a pharmaceutical composition. 
     
     
         23 . A pharmaceutical composition, food additive or dietary supplement, comprising a composition according to any of  claims 7  to  9 , or a plant sRNA extract as defined in any of  claims 1  to  6  and  9 ,
 preferably 
 wherein the pharmaceutical composition, food additive or dietary supplement comprises a) lipids, more preferably at least one liposome, or b) an exosome. 
 
     
     
         24 . A food product comprising a plant sRNA extract, preferably a plant sRNA extract as defined in any of  claims 1  to  6  and  9 , or a composition according to any of  claims 7  to  9 . 
     
     
         25 . A method for producing a second food product, comprising adding to a first food product a plant sRNA extract, preferably a plant sRNA extract as defined in any of  claims 1  to  6  and  9 , or a composition according to any of  claims 7  to  9 . 
     
     
         26 . A plant sRNA extract, preferably as defined in any of  claims 2  to  6  and  9 , or composition comprising 2 or more plant sRNA extracts according to any of  claims 7  to  9 , for use as a medicament.