Therapeutic oligonucleotides
Methods and compositions are provided for oligonucleotides that bind targets of interest. The targets include cells and microvesicles, such as those derived from various diseases. The oligonucleotides can be used for diagnostic and therapeutic purposes. The target of the oligonucleotides can be a target such as PARP1, HIST1H1B, HIST1H1D, NCL, FBL, SFPQ, RPL12, ACTB, HIST1H4A, SSBP1, NONO, H2AFJ, and DDX21, or a complex, subunit or fragment thereof.
1. An oligonucleotide attached to a cytotoxic moiety or a therapeutic agent or a diagnostic agent, wherein the oligonucleotide comprises a sequence according to SEQ ID NO: 4357.
2. The oligonucleotide of claim 1 , wherein the cytotoxic moiety is selected from the group consisting of vinblastine hydrazide, calicheamicin, vinca alkaloid, a cryptophycin, a tubulysin, dolastatin-10, dolastatin-15, auristatin E, rhizoxin, epothilone B, epithilone D, a taxoid, and an maytansinoid.
3. The oligonucleotide of claim 1 , wherein the cytotoxic moiety comprises a protein toxin.
4. The oligonucleotide of claim 3 , wherein the protein toxin is selected from the group consisting of diphtheria toxin, ricin, abrin, gelonin, and Pseudomonas exotoxin A.
5. The oligonucleotide of claim 1 , wherein the therapeutic agent is selected from the group consisting of a tyrosine kinase inhibitor, kinase inhibitor, radionuclide, adriamycin, ansamycin, antibiotic, asparaginase, bleomycin, busulphan, cisplatin, carboplatin, carmustine, capecotabine, chlorambucil, cytarabine, cyclophosphamide, camptothecin, dacarbazine, dactinomycin, daunorubicin, dexrazoxane, docetaxel, doxorubicin, etoposide, epothilones, floxuridine, fludarabine, fluorouracil, gemcitabine, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine, mechlorethamine, mercaptopurine, melphalan, methotrexate, rapamycin (sirolimus), mitomycin, mitotane, mitoxantrone, nitrosurea, paclitaxel, pamidronate, pentostatin, plicamycin, procarbazine, rituximab, streptozocin, teniposide, thioguanine, thiotepa, taxanes, vinblastine, vincristine, vinorelbine, taxol, combretastatin, discodermolide, transplatinum, anti-vascular endothelial growth factor compound, anti-epidermal growth factor receptor compound, and 5-fluorouracil.
6. The oligonucleotide of claim 1 , attached to the diagnostic agent.
7. The oligonucleotide of claim 6 , wherein the diagnostic agent comprises a nanoparticle, liposome, gold, magnetic label, fluorescent label, light emitting particle, or radioactive label.
8. A method of imaging a cell or tissue, comprising
contacting the cell or tissue with the oligonucleotide of claim 6 and detecting the oligonucleotides in contact with the cell or tissue, thereby imaging the cell or tissue.
9. The method of claim 8 , wherein the cell or tissue comprises neoplastic, malignant, tumor, hyperplastic, or dysplastic cells.
10. The method of claim 8 , wherein the tissue comprises lymphoma, leukemia, renal carcinoma, sarcoma, hemangiopericytoma, melanoma, abdominal cancer, gastric cancer, colon cancer, cervical cancer, prostate cancer, pancreatic cancer, breast cancer, or non-small cell lung cancer.
11. The method of claim 8 , wherein the cell or tissue is in vivo, and the contacting comprises administrating the oligonucleotide to a subject.
12. A pharmaceutical composition comprising a therapeutically effective amount of the oligonucleotide of claim 1 attached to the cytotoxic moiety or a therapeutic agent, or a salt thereof, and a pharmaceutically acceptable carrier, diluent, or both.
13. A method of treating or ameliorating a disease or disorder in a subject in need thereof, comprising administering the pharmaceutical composition of claim 12 to the subject.
14. The method of claim 13 , wherein the administering comprises at least one of intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intracerebral, intravaginal, transdermal, rectal, by inhalation, topical administration, or any combination thereof.