US2015344537A1PendingUtilityA1

Non-Transgene Transfection for Therapeutic Purposes

41
Individually held — no corporate assignee on recordPriority: Jan 11, 2013Filed: Jan 10, 2014Published: Dec 3, 2015
Est. expiryJan 11, 2033(~6.4 yrs left)· nominal 20-yr term from priority
Inventors:Mark C. HerzbergKaren Farnie RossBrent R. Sorenson
A61P 37/04A61P 31/00A61P 31/10A61P 31/04A61P 43/00A61P 35/00C12N 2840/203C07K 14/47A61K 48/00A61K 48/005C12N 15/87Y02A50/30
41
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Claims

Abstract

This disclosure describes compositions and methods involved in tumor suppression and inhibiting infection of cells by pathogens. Generally, the compositions include an mRNA cargo that can provide a therapeutic benefit after being introduced into an epithelial cell. In some cases, the mRNA can encode a polypeptide. In some cases, the polypeptide can suppress epithelial cell proliferation. In other embodiments, the polypeptide can be involved in innate immunity. In various embodiments, the polypeptide can include cathelicin antimicrobial protein (CAMP), calprotectin, S100A8, S100A9, a β-defensin, S100A7, secretory leukocyte inhibitor, lipocalin 2, or lysozyme. In some embodiments, the mRNA can include a stabilizing moiety such as, for example, a 5′ cap or a 3′ extension.

Claims

exact text as granted — not AI-modified
1 . A method comprising:
 introducing into an epithelial cell an mRNA encoding a polypeptide involved in suppressing cell proliferation; and   permitting the cell to express the polypeptide in an amount effective to decrease the likelihood that the cell proliferates in an anchorage-independent environment.   
     
     
         2 . The method of  claim 1  wherein the polypeptide comprises calprotectin, S100A8, or S100A9. 
     
     
         3 . A method comprising:
 introducing into a cell an mRNA encoding a polypeptide involved in innate immunity; and   permitting the cell to express the polypeptide in an amount effective to decrease the likelihood that the cell is infected by a pathogen.   
     
     
         4 . The method of  claim 3  wherein the polypeptide comprises cathelicin antimicrobial protein (CAMP), calprotectin, S100A8, S100A9, a β-defensin, S100A7, secretory leukocyte inhibitor, lipocalin 2, or lysozyme. 
     
     
         5 . The method of  claim 3 , wherein the mRNA comprises a stabilizing moiety. 
     
     
         6 . The method of  claim 5  wherein the stabilizing moiety comprises a 5′ cap. 
     
     
         7 . The method of  claim 5  wherein the stabilizing moiety comprises a 3′ extension. 
     
     
         8 . The method of  claim 1 , wherein the cell is a mucosal epithelial cell. 
     
     
         9 . The method of  claim 3  further comprising permitting the cell to be exposed to the pathogen. 
     
     
         10 . The method of  claim 3  wherein the pathogen comprises a bacterium. 
     
     
         11 . The method of  claim 10  wherein the bacterium comprises  Capnocytophaga sputigena, Escherichia coli , a  Staphylococcus  spp., a  Streptococcus  spp.,  Listeria monocytogenes, Salmonella typhimurium, Borrelia burgdorferi, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Pseudomonas aeruginosa , a  Chlamydia  spp., a  Neisseria  spp., a  Gardnerella  spp., or a  Trichomonas  spp. 
     
     
         12 . The method of  claim 3  wherein the pathogen comprises a fungus. 
     
     
         13 . The method of  claim 12  wherein the fungus comprises fungi  Candida albicans, Acinetobacter baumannii , or an  Aspergillus  spp. 
     
     
         14 . The method of  claim 3  wherein the cell is a cell of a subject having or at risk of having a condition caused by infection by the pathogen. 
     
     
         15 . The method of  claim 14  wherein the condition comprises a carcinoma. 
     
     
         16 . The method of  claim 3  further comprising washing the cell to remove mucosal fluid from the cell prior to introducing the mRNA into the cell. 
     
     
         17 . The method of  claim 16  wherein the mucosal fluid comprises saliva. 
     
     
         18 . A composition comprising:
 an mRNA that encodes a polypeptide that suppresses cell proliferation in an epithelial cell; and   an in vivo delivery vehicle.   
     
     
         19 . The composition of  claim 18  wherein the polypeptide comprises calprotectin, S100A8, or S100A9. 
     
     
         20 . The composition of  claim 18  wherein the polypeptide suppresses cell proliferation of the epithelial cell when the epithelial cell is grown in an anchorage-independent environment. 
     
     
         21 . A composition comprising:
 an mRNA that encodes a polypeptide involved in innate immunity; and   an in vivo delivery vehicle.   
     
     
         22 . The composition of  claim 21  wherein the polypeptide comprises cathelicin antimicrobial protein (CAMP), calprotectin, S100A8, S100A9, a β-defensin, S100A7, secretory leukocyte inhibitor, lipocalin 2, or lysozyme. 
     
     
         23 . The composition of  claim 21  wherein the mRNA comprises a stabilizing moiety. 
     
     
         24 . The composition of  claim 23  wherein the stabilizing moiety comprises a 5′ cap. 
     
     
         25 . The composition of  claim 23  wherein the stabilizing moiety comprises a 3′ extension.

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