Use of magnesium (mg2+) for the preparation of a therapeutic composition for transfection of a polynucleotide into a cell and compositions useful in gene therapy

Abstract

Described is the use of magnesium (Mg 2+ ) for the preparation of a therapeutic composition for the introduction of a polynucleotide into a cell in vivo.

1 . Use of magnesium (Mg 2+ ) for the preparation of a therapeutic composition for the in vivo transfection of a polynucleotide into a cell.  
     
     
         2 . The use of  claim 1 , wherein said magnesium is magnesium chloride (MgCl 2 ).  
     
     
         3 . The use of  claim 1  or  2 , wherein said therapeutic composition contains between from about 0.1 to about 100 mM preferably from about 0.1 to about 10 mM of magnesium (Mg 2+ ).  
     
     
         4 . The use of any one of  claims 1  to  3 , wherein said therapeutic composition is for administration into a vertebrate target tissue.  
     
     
         5 . The use of  claim 4 , wherein said administration is made by intradermal, subdermal, intravenous, intramuscular, intranasal, intracerebral, intratracheal, intraarterial, intraperitoneal, intravesical, intrapleural, intracoronary or intratumoral injection.  
     
     
         6 . The use of  claim 4 , wherein said administration is made into the lung by inhalation or aerosol administration.  
     
     
         7 . The use of  claim 4 , wherein said target tissue is muscle.  
     
     
         8 . The use of any one of  claims 4  to  7 , wherein the administration of magnesium (Mg 2+ ) is performed independently from a second administration consisting in administration of a composition containing at least one polynucleotide into the same target tissue.  
     
     
         9 . The use of  claim 8 , wherein the administration of magnesium (Mg 2+ ) is performed prior to said second administration.  
     
     
         10 . The use of any one of  claims 1  to  7 , wherein said therapeutic composition further comprises at least one polynucleotide.  
     
     
         11 . The use of any one of  claims 1  to  10 , wherein said polynucleotide contains a gene and is capable of functionally expressing said gene in said cell.  
     
     
         12 . The use of  claim 10  or  11 , wherein said polynucleotide is naked.  
     
     
         13 . The use of  claim 10  or  11 , wherein said polynucleotide is complexed with cationic components, more preferably with cationic lipids.  
     
     
         14 . The use of any one of  claims 10  to  13 , wherein the said polynucleotide concentration ranges from about 0.1 μg/ml to about 20 mg/ml.  
     
     
         15 . The use of  claim 11 , wherein said gene encodes all or part of dystrophin or cystic fibrosis transmembrane conductance regulator (CFTR) polypeptides.  
     
     
         16 . The use of any one of  claims 1  to  15 , wherein said composition further comprises at least one component selected from the group consisting of chloroquine, protic compounds such as propylene glycol, polyethylene glycol, glycerol, ethanol, 1-methyl L-2-pyrrolidone or derivatives, aprotic compounds such as dimethylsulfoxide (DMSO), diethylsulfoxide, di-n-propylsulfoxide, dimethylsulfone, sulfolane, dimethylformamide, dimethylacetamide, tetramethylurea, acetonitrile or derivatives.  
     
     
         17 . The use of any one of  claims 1  to  16 , wherein said composition further comprises at least one component selected from the group consisting of cytokines and actin-G.  
     
     
         18 . The use of any one of  claims 1  to  17 , wherein the therapeutic composition further comprises a pharmaceutically acceptable injectable carrier.  
     
     
         19 . A process for transfecting a polynucleotide into cells wherein said process comprises contacting said cells with at least one composition comprising magnesium (Mg 2+ ) before, simultaneously or subsequently to contacting it with the polynucleotide.  
     
     
         20 . The process of  claim 19 , wherein the cells are first contacted with the magnesium (Mg 2+ ) and subsequently with the polynucleotide.  
     
     
         21 . Use of magnesium (Mg 2+ ) for improving transfection in vivo of a polynucleotide into a cell.