Boranophosphate siRNA-aptamer chimeras for tumor-specific downregulation of cancer receptors and modulators.
There is a need for novel, effective, and cell- and gene-specific therapeutics for cancer. Modified oligonucleotides can be used to modulate specifically and potently the expression of several genes that are upregulated in breast and prostate cancer and have been found to be causal to the tumor phenotype. Synergistic downregulation of these genes may be a potent therapeutic intervention. We are investigating the use of boranophosphate (BP) analogues of RNA as promising candidates for enhancing the potential of three relatively new, gene-specific, anticancer strategies: (1) Tumor-targeted borane siRNA against a combination of genes that control metabolism and transduction; (2) Tumor-specific modified aptamers against prostate specific membrane antigen (PSMA) and ERB2 in breast cancer as delivery agents; and (3) Cancer cell obliteration by cell-specific radiation therapy: Boron-Neutron-Capture-Therapy.
Shaw
Barbara Ramsay
BR
Department of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708-0346, USA. brshaw@chem.duke.edu
Moussa
Laura
L
Sharaf
Mariam
M
Cheek
Marcus
M
Dobrikov
Mikhail
M
D000954:Antigens, Surface / Q000235:genetics; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001880:Boranes / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy; D001943:Breast Neoplasms / Q000628:therapy; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D010710:Phosphates / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
D000954:Antigens, Surface; D052157:Aptamers, Nucleotide; D001880:Boranes; D043425:Glutamate Carboxypeptidase II; D010710:Phosphates; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C510710:boranophosphate; C473848:FOLH1 protein, human