Oligonucleotide therapeutics oligonucleotides

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. 

An effective therapeutic agent must also have the abiUty to reach its target sequence m vivo. BioavailabiUty requires that the antisense oligonucleotide be able to pass through the cell membrane, and that it have a low affinity for nontarget cellular compartments and, in animal systems, nontarget organs. 

Uhlman E., Peyman, a. Antisense oligonucleotides A new therapeutic principle. Chem. Rev. 1990 90 544. 

Nucleotides and nucleic acids are critical tools in the areas of gene expression, therapeutics, and diagnostics. However, there are certain challenges associated with their large-scale purification and subsequent characterization. While solid-state oligonucleotide synthesis is relatively simple and can be totally automated, intra- and intermolecular associations may occur involving shorter sequences that may hybridize with the desired full length... 

The potential of the chemically modified nucleic acid molecules has been proven by in vitro studies however, the in vivo therapeutic applicability of these molecules seems to be unsatisfactory because of their possible toxic effects (largely unknown) and adverse bioavailability. In this view, both antisense and transfection technologies require reliable and efficient systems for their delivery into target cells. On the basis of this consideration, the development of an efficient nucleic acid delivery system represents one of the key steps for these therapeutic agents, which are necessary for a practical clinical utilization of natural or unnatural oligonucleotides. 

Uhlmann, E., and Peyman, A., Antisense oligonucleotides a new therapeutic principle, Chemical Reviews, 1990, 90, 543-584. 

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... 

Orr, R. and O Neill, C. 2000. Patent review therapeutic applications of antisense oligonucleotides, 1999-2000. 

Galderisi, U., Cipollaro, M., and Cascino, A. 2001. Antisense oligonucleotides as drugs for HIV treatment. Expert Opinion on Therapeutic Patents 11(10), 1605-1611. 

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