Therapeutic aptamers

Some oligonucleotide therapeutics (aptamers) have been designed specifically to inhibit clotting, and for those compounds the anticoagulant effects are more pronounced, as intended. The doses used in toxicity studies are designed to characterize the superpharmacology of these agents. 

Many parallels may be seen between therapeutic aptamers and therapeutic antibodies. 

Bouchard, P.R., Hutabarat, R.M., and Thompson, K.M. Discovery and development of therapeutic aptamers. Annual Review of Pharmacology and Toxicology 50,237-257,2010. 

Bruno, J.G., 2013. A review of therapeutic aptamer conjugates with emphasis on new approaches. Pharmaceuticals 6 (3), 340-357. 

By similar logic, protein affinity Hbraries have been constmcted to identify protein—protein combining sites, as in antibody—antigen interaction (19) and recombinant Hbraries have been made which produce a repertoire of antibodies in E. coli (20). In another case, a potential DNA-based therapeutic strategy has been studied (21). DNAs from a partially randomized Hbrary were selected to bind thrombin in vitro. Oligonucleotides, termed aptamers that bound thrombin shared a conserved sequence 14—17 nucleotides long. 

Ulrich H, Trujillo CA, Nery AA, Alves JM, Majumder P, Resende RR, Martins AH (2006) DNA and RNA aptamers from tools for basic research towards therapeutic applications. Comb Chem Fligh Throughput Screen 9 619-632... 

Oligonucleotide-based drugs such as antisense drugs, aptamers, and small interfering RNA (siRNA) have attracted considerable attention as promising therapeutic agents for the treatment of various human diseases [59], To develop... 

Nimjee, S.M., Rusconi, CP., and Sullenger, B.A. 2005. Aptamers an emerging class of therapeutics. Annual Review of Medicine 56, 555-583. 

Also, high-throughput screening of small ligands for proteins [53] or other biomacromolecules of therapeutic interest can be done with the aid of aptamers. Because small molecules replace an ap tamer in its complex with the macromolecule, this substitution can be monitored by a change of fluorescence anisotropy of labeled ap tamer or by a change in the activity of an aptazyme. 

In vitro selection generates RNA and DNA sequences that can bind to target molecules with extremely high affinity and specificity. Aptamers are considered as a promising class of compounds with a wide range of application in therapeutics (Famulok et al., 2000 Toulme, 2000 White et al., 2000), diagnostics (Brody et... 

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