Mfold web server for nucleic acid folding and hybridization prediction. Generation of species cross-reactive aptamers using “toggle” SELEX. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Antidote-mediated control of an anticoagulant aptamer in vivo. Blocking the initiation of coagulation by RNA aptamers to factor VIIa. Rusconi, C.P., Yeh, A., Lyerly, H.K., Lawson, J.H. ![]() Antidote-controlled platelet inhibition targeting von Willebrand factor with aptamers. RNA aptamers as reversible antagonists of coagulation factor IXa. A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery. Adverse drug events in hospitalized cardiac patients. The potential of aptamers as anticoagulants. Nimjee, S.M., Rusconi, C.P., Harrington, R.A. Technology, development and clinical application. Nucleic acid aptamers in therapeutic anticoagulation. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. In vitro selection of RNA molecules that bind specific ligands. Safety and efficacy of a lentiviral vector containing three anti-HIV genes-CCR5 ribozyme, tat-rev siRNA, and TAR decoy-in SCID-hu mouse–derived T cells. ![]() Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Sullenger, B.A., Gallardo, H.F., Ungers, G.E. Aptamers: an emerging class of therapeutics. Multivalent 4–1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165. ![]() First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity. The availability of universal antidotes to control the activity of any aptamer suggests that aptamers may be a particularly safe class of therapeutics.ĭyke, C.K. We show that protein- and polymer-based molecules that capture oligonucleotides can reverse the activity of several aptamers in vitro and counteract aptamer activity in vivo. These universal antidotes exploit the fact that, when systemically administered, aptamers are the only free extracellular oligonucleotides found in circulation. Here we describe the development of a set of antidote molecules that are capable of counteracting the effects of an entire class of therapeutic agents based upon aptamers. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive to generate antidotes for most therapeutic agents. With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater.
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