Bispecific aptamer for treating cancer
View Patent ↗Bispecific aptamers having a first end that specifically binds to a first tumor specific marker, tumor antigen, or viral protein and a second end that specifically binds to a second tumor specific marker, tumor antigen, or viral protein are provide. The bispecific aptamers can be used to treat cancer or virally infected cells. Generally, the bispecific aptamers bind to two surface proteins, preferably different proteins, on the same cell. In a preferred embodiment the bispecific aptamers bind to two different tumor markers, tumor antigens, tumor specific proteins and combinations thereof.
1. A bispecific aptamer comprising a first end that specifically binds to a first tumor specific marker and a second end that specifically binds to a second tumor specific marker, wherein the first tumor specific marker is EpCAM and the second tumor specific marker is CD44, and further comprising one or more siRNA that downregulate an oncogene and wherein the oncogene is encoded by an oncogene selected from the group consisting of ABL1, ABL2, AKT1, AKT2, ATF1, BCL11A, BCL2, BCL3, BCL6, BCR, BRAF, CARD11, CBLB, CBLC, CCND1, CCND2, CCND3, CDX2, CTNNB1, DDB2, DDIT3, DDX6, DEK, ELK4, ERBB2, ETV4, ETV6, EVI1, EWSR1, FEV, FGFR1, FGFR1OP, FGFR2, FUS, GOLGA5, GOPC, HMGA1, HMGA2, HRAS, IRF4, JUN, KIT, KRAS, LCK, LMO2, MAF, MAFB, MAML2, MDM2, MET, MITF, MPL, MYB, MYC, MYCL1, MYCN, NCOA4, NFKB2, NRAS, NTRK1, NUP214, PAX8, PDGFB, PIK3CA, PIM1, PLAG1, PPARG, PTPN11, RAF1, REL, RET, ROS1, SMO, SS18, TCL1A, TET2, TFG, MLL, TLX, TPR, and USP6.
2. The bispecific aptamer of claim 1 , further comprising an unpaired linker.
3. The bispecific aptamer of claim 1 , wherein the oncogene comprises AKT1.
4. The bispecific aptamer of claim 1 , wherein the oncogene comprises BRAF.
5. The bispecific aptamer of claim 1 , wherein the aptamer includes 2′ fluoro-modified nucleotides.
6. A composition comprising a bispecific aptamer having a first end that specifically binds to tumor specific marker EpCAM and a second end that specifically binds to tumor specific marker CD44 and further comprising one or more siRNA that downregulate an AKT1 oncogene and wherein the composition further comprises a pharmaceutically acceptable excipient.
7. The composition of claim 6 wherein the bispecific aptamer is administered to a subject in need thereof in an amount effective to inhibit or reduce tumor growth.
8. The composition of claim 7 wherein the bispecific aptamer is administered in an amount effective to inhibit or reduce ovarian tumor growth.