Pharmaceutical composition for preventing or treating liver cancer

Abstract

The present invention provides siRNA or dsRNA, which can effectively inhibit the expression of three highly expressed markers in liver cancer, and a pharmaceutical composition including the same can obtain excellent effects of preventing or treating liver cancer through RNAi. A pharmaceutical composition for preventing or treating liver cancer according to an embodiment of the present invention includes at least one of siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 5 to 157, and an antisense RNA having a complementary sequence thereto and dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 158 to 310.

1 . A pharmaceutical composition for preventing or treating liver cancer, comprising at least one of the followings:
 siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 5 to 157, and an antisense RNA having a complementary sequence thereto; and   dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 158 to 310.   
     
     
         2 . The composition according to  claim 1 , wherein the composition comprises at least one of the followings:
 siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 5 to 12, 14 to 19, 21, 23, 24, 26, 28 to 34, 35 to 37, 39 to 41, 43, 45 to 47, 49 to 53, 55 to 60, 62 to 73, 75 to 81, 84 to 87, 89 to 98, 100 to 102, 105 to 116, 118 to 128, 130 to 154, 156 to 157, and an antisense RNA having a complementary sequence thereto; and   dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 158 to 165, 167 to 172, 174, 176, 177, 179, 181 to 187, 188 to 190, 192 to 194, 196, 198 to 200, 202 to 206, 208 to 213, 215 to 226, 228 to 234, 237 to 240, 242 to 251, 253 to 255, 258 to 269, 271 to 281, 283 to 307, 309 and 310.   
     
     
         3 . The composition according to  claim 1 , wherein the composition comprises at least one of the followings:
 siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 5 to 28, and an antisense RNA having a complementary sequence thereto; and   dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 158 to 181.   
     
     
         4 . The composition according to  claim 1 , wherein the composition comprises at least one of the followings:
 siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 29 to 55, and an antisense RNA having a complementary sequence thereto; and   dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 182 to 208.   
     
     
         5 . The composition according to  claim 1 , wherein the composition comprises at least one of the followings:
 siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 56 to 120, and an antisense RNA having a complementary sequence thereto; and   dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 209 to 273.   
     
     
         6 . The composition according to  claim 1 , wherein the composition comprises at least one of the followings:
 siRNA which includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 121 to 157, and an antisense RNA having a complementary sequence thereto; and   dsRNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 274 to 310.   
     
     
         7 . The composition according to  claim 1 , wherein the siRNA or dsRNA is loaded on at least one carrier selected from the group consisting of liposomes, lipofectamines, dendrimers, micelles, porous silica particles, amino clay, gold nanoparticles, magnetic nanoparticles, graphene, oxidized graphene, chitosan, dextran, pectin, manganese dioxide two-dimensional sheet, PVA, gelatin, silica, glass particles, protamine, exosome, polyethyleneimine, N-butyl cyanoacrylate, gel foam, ethanol, nanocrystals, nanotubes, carbon nanoparticles, hyaluronic acid, iron oxide, polylactic acid, polybutyl cyanoacrylate, albumin, lipid particles, polyethylene glycol, poly-L-guluronic alginate, polyglycolic-polyacticpolyactic acid, polydioxanone, polyglycolic acid-co-caprolactone, polypropylene and hydrogel. 
     
     
         8 . The composition according to  claim 7 , wherein the carrier is a porous silica particle characterized in that t when a ratio of absorbance in the following Equation 1 becomes ½ is 20 or more:
   A t /A 0    [Equation 1]
 
 wherein A 0  is absorbance of the porous silica particle measured by placing 5 ml of a suspension including 1 mg/ml of the porous silica particle into a cylindrical dialysis membrane having pores with a diameter of 50 kDa; 
 15 ml of the same solvent as the suspension is placed outside the dialysis membrane while being in contact with the dialysis membrane, followed by horizontal agitation at 60 rpm and 37° C. inside and outside the dialysis membrane; and 
 A t  is absorbance of the porous silica particle measured after t hours elapses from the measurement of A o . 
 
     
     
         9 . The composition according to  claim 8 , wherein the t is 40 or more. 
     
     
         10 . The composition according to  claim 8 , wherein the siRNA includes a sense RNA having at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 28, 119 and 136, and an antisense RNA having a complementary sequence thereto; and
 the dsRNA has at least one sequence selected from the group consisting of sequences of SEQ ID NOs: 181, 272 and 289.   
     
     
         11 . The composition according to  claim 8 , wherein the porous silica particle has a hydrophilic substituent or a hydrophobic substituent. 
     
     
         12 . The composition according to  claim 8 , wherein the porous silica particle has at least one hydrophilic substituent selected from the group consisting of aldehyde, keto, carbamate, sulfate, sulfonate, amino, amine, aminoalkyl, silyl, carboxyl, sulfonic acid, thiol, ammonium, sulfhydryl, phosphate, ester, imide, thioimide, ether, indene, sulfonyl, methylphosphonate, polyethylene glycol, substituted or unsubstituted C 1  to C 30  alkyl, substituted or unsubstituted C3 to C30 cycloalkyl, substituted or unsubstituted C 6  to C 30  aryl, and C 1  to C 30  ester groups. 
     
     
         13 . The composition of  claim 8 , wherein the porous silica particle is positively or negatively charged on an outer surface of the particle or an inside of a pore thereof at neutral pH. 
     
     
         14 . The composition of  claim 8 , wherein the porous silica particle is positively charged on an outer surface of the particle or an inside of a pore thereof at neutral pH. 
     
     
         15 . The composition of  claim 8 , wherein the porous silica particle has an average particle diameter of 100 to 400 nm and a pore diameter of 4 to 30 nm.