Biologically tolerated low molecular weight polyethylenimines

Abstract

The invention relates to low molecular weight polyethylenimines, to vectors for inserting nucleic acids into cells which contain low molecular weight polyethylenimines, and to the preparation and use of the low molecular weight polyethylenimine and the vector. The invention relates to a vector for inserting a nucleic acid into a cell, which vector contains a low molecular weight polyethylenimine (LMW PEI) and a nucleic acid, with the LMW PEI having a molecular weight of less than 50,000 Da.

1 - 33 . (canceled) 
     
     
         34 . A vector for inserting a nucleic acid into a cell, which vector contains a low molecular weight polyethylenimine (LMW PEI) and a nucleic acid, with the LMW PEI having a molecular weight of less than 50,000 Da. 
     
     
         35 . A vector as claimed in  claim 34 , wherein the LMW PEI has a molecular weight selected from the group consisting of: (1) 500 to 30,000 Da; (2) 1000 to 5000 Da; and (3) about 2000 Da. 
     
     
         36 . A vector as claimed in  claim 34 , wherein the nucleic acid is a viral or nonviral nucleic acid construct. 
     
     
         37 . A vector as claimed in  claim 34 , wherein the nucleic acid construct contains one or more effector genes. 
     
     
         38 . A vector as claimed in  claim 34 , wherein at least one effector gene encodes: (1) a pharmacological active compound or its prodrug form; or (2) an enzyme. 
     
     
         39 . A vector as claimed in one or more of  claim 34 , wherein at least one effector gene is expressed together with a cell-specific ligand as a fusion protein. 
     
     
         40 . A vector as claimed in  claim 34 , wherein the LMW PEI is coupled to a cell-specific ligand. 
     
     
         41 . A vector as claimed in  claim 40 , wherein the cell-specific ligand binds to the outer membrane of a target cell. 
     
     
         42 . A vector as claimed in  claim 34 , wherein the target cell is an endothelial cell, a muscle cell, a macrophage, a lymphocyte, a glia cell, an hematopoietic cell, a tumor cell, a virus-infected cell, a bronchial epithelial cell or a liver cell. 
     
     
         43 . A vector as claimed in  claim 34 , wherein the ratio by weight of LMW PEI to nucleic acid is selected from the group of ranges consisting of: (1) 3:1 or more and (2) 8:1 or more. 
     
     
         44 . A low molecular weight polyethylenimine which has a molecular weight of less than 50,000 Da and which is prepared by a process which comprises monomeric ethylenimine being polymerized in aqueous solution by adding hydrochloric acid.
 wherein,   (i) the aqueous solution is from 0.1% strength to 90% strength with respect to monomeric ethylenimine and from 0.1% strength to 10% strength with respect to concentrated hydrochloric acid;   (ii) the polymerization is carried out at a reaction temperature of from 30° C. to 70° C.; and   (iii) the reaction time is from 1 to 30 days.   
     
     
         45 . A process for preparing a vector according to  claim 34 , which comprises mixing an appropriate quantity of LMW PEI with an appropriate quantity of nucleic acid in an aqueous solution. 
     
     
         46 . A method of inserting a nucleic acid into a cell which comprises of using the vector of  claim 34  to insert the nucleic acid and wherein the cell is an endothelial cell, a lymphocyte, a macrophage, a liver cell, a fibroblast, a muscle cell or an epithelial cell. 
     
     
         47 . The method of  claim 46 , wherein the cell becomes a transfected cell, and comprises incubating the vector in vitro with a cell. 
     
     
         48 . A transfected cell which contains a vector as claimed in  claim 34 . 
     
     
         49 . A pharmaceutical composition which comprises: (1) a vector for inserting a nucleic acid into a cell, which vector contains a low molecular weight polyethylenimine (LMW PEI) and a nucleic acid, with the LMW PEI having a molecular weight of less than 50,000 Da; (2) a low molecular weight polyethylenimine which has a molecular weight of less than 50,000 Da; or (3) a transfected cell which contains a vector as claimed in  claim 34 . 
     
     
         50 . A process for preparing the pharmaceutical composition of  claim 49 , which comprises mixing a nucleic acid with an LMW PEI.