Nucleic acid-containing complex

Abstract

A nucleic acid-containing complex, containing a nucleic acid and a biodegradable polymer, especially a positively-charged water-insoluble biodegradable polymer, is disclosed. The complex has excellent properties of sustainedly releasing a desired nucleic acid, especially DNA, to a site in need of a treatment. Since the complex can be taken up to phagocytes such as macrophages and delivered specifically to the target site, the function of the nucleic acid can be exhibited in a target site specific manner, and thus more specific gene therapy can be achieved. The complex has no adverse effects, such as occurrence of recombinants or toxicity which could be caused by using a virus vector such as adenovirus, or liposome. Thus, the complex is particularly preferable for the field of gene therapy. Furthermore, the complex enhances the biological effect of the nucleic acid introduced into the cells, allowing a gene therapy with a lower dose of nucleic acids.

1 . A nucleic acid-containing complex comprising a nucleic acid and a positively-charged water-insoluble biodegradable polymer, wherein said nucleic acid can be released by degradation of the biodegradable polymer. 
     
     
         2 . The nucleic acid-containing complex according to  claim 1  wherein said positively-charged water-insoluble biodegradable polymer comprises an introduced positively-charged group. 
     
     
         3 . The nucleic acid-containing complex of  claim 1 , wherein said positively-charged water-insoluble biodegradable polymer comprises at least one member selected from the group consisting of collagen, gelatin, chitin, chitosan, hyaluronic acid, alginic acid, starch, and a derivative thereof. 
     
     
         4 . The nucleic acid-containing complex of  claim 3 , wherein said derivative comprises an amino derivative. 
     
     
         5 . The nucleic acid-containing complex of  claim 1 , wherein said positively-charged water-insoluble biodegradable polymer comprises a crosslinked gelatin which has an introduced positively-charged group. 
     
     
         6 . The nucleic acid-containing complex of  claim 1 , wherein said nucleic acid comprises at least one member selected from the group consisting of a plasmid DNA, an oligonucleotide, and a double-stranded nucleic acid compound. 
     
     
         7 . The nucleic acid-containing complex of  claim 6 , wherein said nucleic acid comprises at least one member selected from the group consisting of vascular endothelial growth factor gene, hepatocyte growth factor gene, and fibroblast growth factor gene. 
     
     
         8 . The nucleic acid-containing complex of  claim 7 , wherein said fibroblast growth factor gene comprises SEQ. ID No. 1. 
     
     
         9 . A pharmaceutical composition comprising as an active ingredient a nucleic acid-containing complex comprising a nucleic acid and a positively-charged water-insoluble biodegradable polymer, wherein said nucleic acid can be released by degradation of said biodegradable polymer. 
     
     
         10 . The pharmaceutical composition of  claim 9 , which is used for gene therapy. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein said gene therapy is achieved by local administration of the gene. 
     
     
         12 . A method for controlling a rate of nucleic acid release comprising:
 incorporating a nucleic acid into a positively-charged water-insoluble biodegradable polymer; and   allowing the nucleic acid to be released by degradation of said biodegradable polymer.   
     
     
         13 . The method for controlling a rate of nucleic acid release according to  claim 12   wherein said positively-charged water-insoluble biodegradable polymer comprises an introduced positively-charged group.   
     
     
         14 . The method of  claim 12 , wherein said positively-charged water-insoluble biodegradable polymer comprises at least one member selected from the group consisting of collagen, gelatin, chitin, chitosan, hyaluronic acid, alginic acid, starch, and a derivative thereof. 
     
     
         15 . The method of  claim 14 , wherein said derivative comprises an amino derivative. 
     
     
         16 . The method of  claim 12 , wherein said positively-charged water-insoluble biodegradable polymer comprises a crosslinked gelatin having an introduced positively-charged group. 
     
     
         17 . The method of  claim 12 , wherein said nucleic acid comprises at least one member selected from the group consisting of a plasmid DNA, an oligonucleotide, and a double-stranded nucleic acid compound. 
     
     
         18 . The method of  claim 17 , wherein said nucleic acid comprises at least one member selected from the group consisting of vascular endothelial growth factor gene, hepatocyte growth factor gene, and fibroblast growth factor gene. 
     
     
         19 . The method of  claim 18 , wherein said fibroblast growth factor gene comprises DNA comprising SEQ. ID No. 1. 
     
     
         20 . A method for enhancing the function of a nucleic acid, comprising:
 incorporating a nucleic acid into a positively-charged water-insoluble biodegradable polymer; and   allowing the nucleic acid to be released by degradation of the biodegradable polymer to exhibit the function of the nucleic acid.   
     
     
         21 . The method for enhancing function of a nucleic acid according to  claim 20   wherein said positively-charged water-insoluble biodegradable polymer comprises an introduced positively-charged group.   
     
     
         22 . The method of  claim 20 , wherein said positively-charged water-insoluble biodegradable polymer comprises at least one member selected from the group consisting of collagen, gelatin, chitin, chitosan, hyaluronic acid, alginic acid, starch, and a derivative thereof. 
     
     
         23 . The method of  claim 22 , wherein said derivative comprises an amino derivative. 
     
     
         24 . The method of  claim 20 , wherein said positively-charged water-insoluble biodegradable polymer comprises a crosslinked gelatin having an introduced positively-charged group. 
     
     
         25 . The method of  claim 20 , wherein said nucleic acid comprises at least one member selected from the group consisting of a plasmid DNA, an oligonucleotide, and a double-stranded nucleic acid compound. 
     
     
         26 . The method of  claim 25 , wherein said nucleic acid comprises at least one member selected from the group consisting of vascular endothelial growth factor gene, hepatocyte growth factor gene, and fibroblast growth factor gene. 
     
     
         27 . The method of  claim 26 , wherein said fibroblast growth factor gene comprises SEQ. ID No. 1.