Rna and nucleic acid carrier including the same

Abstract

A nucleic acid carrier according to an embodiment of the present disclosure includes CpG-ODN-RNA conjugate and a porous silica particle carrying the conjugate inside pores thereof. In this regard, the nucleic acid carrier of the present invention can stably deliver loaded nucleic acid molecules to a body and release the same to a target, thereby increasing Type 1 interferon and exhibiting RNA-inherent functions.

What is claimed is: 
     
         1 . A nucleic acid carrier, comprising:
 a CpG oligodeoxynucleotide-RNA (CpG-ODN-RNA) conjugate; and   a porous silica particle carrying the CpG-ODN-RNA conjugate inside pores thereof, the porous silica particle having an average pore diameter of 7 to 30 nm, the porous silica particle having a zeta potential of 20 to 80 mV.   
     
     
         2 . The nucleic acid carrier according to  claim 1 , wherein the RNA is mRNA, tRNA, miRNA, snRNA, snoRNA, aRNA, siRNA, circular RNA or piRNA. 
     
     
         3 . The nucleic acid carrier according to  claim 1 , wherein the RNA is indoleamine 2,3-dioxygenase (IDO) siRNA. 
     
     
         4 . The nucleic acid carrier according to  claim 1 , wherein the CpG-ODN and the RNA of the CpG-ODN-RNA conjugate are coupled through a linker. 
     
     
         5 . The nucleic acid carrier according to  claim 4 , wherein the linker is at least one selected from the group consisting of a saturated alkyl chain (C3 to C18), a triazole linker, and 4-methyl-6,7,8,9,10,10a-hexahydro-5H-3λ2-cycloocta[d]pyridazine linker. 
     
     
         6 . The nucleic acid carrier according to  claim 3 , wherein the siRNA further comprises a sequence of 1 to 10 nt complementary to IDO mRNA at a N terminal or a C terminal. 
     
     
         7 . The nucleic acid carrier according to  claim 1 , wherein the CpG-ODN is CpG-A ODN, CpG-B ODN or CpG-C ODN. 
     
     
         8 . The nucleic acid carrier according to  claim 1 , wherein the porous silica particle is positively charged inside the pores. 
     
     
         9 . The nucleic acid carrier according to  claim 1 , wherein a weight ratio of the conjugate and the particle ranges from 1: 1 to 1:20. 
     
     
         10 . The nucleic acid carrier according to  claim 1 , wherein a BET surface area of the particle ranges from 200 to 700 m 2 /g, and a particle diameter ranges from 50 to 1000 nm. 
     
     
         11 . A method for treatment of cancer, the method comprising administering the nucleic acid carrier of  claim 3  to a subject in need thereof. 
     
     
         12 . The method according to  claim 11 , wherein the cancer is selected from ovarian cancer, cervical cancer, follicle cysts, gynecologic cancer, urologic cancer, renal cancer, testicular cancer, penile cancer, genitourinary tract cancer, testicular tumor, bladder cancer, skin cancer, sarcoma, osteosarcoma, malignant bone tumor, soft tissue sarcoma, keratoacanthoma, melanoma, lung cancer, small cell lung carcinoma, non-small cell lung carcinoma (NSCLC), lung adenocarcinoma, squamous cell carcinoma of the lung, papillary cancer, breast cancer, triple negative breast cancer (TNBC), breast endocrine cancer, hepatobiliary and pancreatic cancer, liver cancer, cholangiocarcinoma, gallbladder cancer, bile duct cancer, pancreatic cancer, bone cancer, bone marrow disorder, lymphatic disorder, hair cell cancer, oral and pharyngeal (oral) cancer, lip cancer, tongue cancer, oral cancer, salivary gland cancer, pharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, gastrointestinal cancer, small intestine cancer, colon cancer, rectal cancer, prostate cancer, vulvar cancer, thyroid cancer, large intestine cancer, endometrial cancer, uterine cancer, brain cancer, glioma, non-glioma tumor, malignant glioma, metastatic brain cancer, brain parenchyma, vestibular schwannoma, pituitary tumor, head and neck cancer, central nervous system cancer, peritoneal cancer, hepatocellular carcinoma, head cancer, neck cancer, primary tumor, metastatic tumor, lymphoma, squamous cell carcinoma, hematologic malignancy, endocrine cancer, Hodgkin disease or leukemia. 
     
     
         13 . A RNA comprising a siRNA having one of: 
 (1) SEQ ID NOs: 1 and 2;   (2) SEQ ID NOs: 3 and 4;   (3) SEQ ID NOs: 5 and 6;   (4) SEQ ID NOs: 7 and 8; and   (5) SEQ ID NOs: 9 and 10.   
     
     
         14 . The RNA according to  claim 13 , wherein the siRNA further comprises a sequence of 1 to 10 nt complementary to IDO mRNA at a 5′-end or a 3′-end of the siRNA. 
     
     
         15 . The RNA according to  claim 13 , wherein the siRNA further comprises CpG oligodeoxynucleotide (CpG-ODN) coupled to N terminal or C terminal thereof. 
     
     
         16 . The RNA according to  claim 15 , wherein the CpG-oligodeoxynucleotide (ODN) is CpG-A ODN, CpG-B ODN or CpG-C ODN. 
     
     
         17 . The RNA according to  claim 15 , wherein the CpG-ODN comprises any one nucleotide among SEQ ID NOs: 13 to 15. 
     
     
         18 . The RNA according to  claim 15 , wherein CpG-ODN and siRNA are coupled through a linker. 
     
     
         19 . The RNA according to  claim 18 , wherein the linker is saturated alkyl chains (C3 to C18), triazole linker or 4-methyl-6,7,8,9,10,10a-hexahydro-5H-3λ2-cycloocta[d]pyridazine linker. 
     
     
         20 . A siRNA comprising the sequence of SEQ ID NO: 11 and the sequence of SEQ ID NO: 12. 
     
     
         21 . A CpG oligodeoxynucleotide-RNA (CpG-ODN-RNA) conjugate comprising at least one of the sequences of SEQ ID NOs: 13 to 15.