The recent development of in vitro methods to select high-affinity ligands by combinatorial chemistry methodologies promises unique and theoretically unlimited supplies of novel therapeutic and diagnostic reagents. One such combinatorial chemistry process, systematic evolution of ligands by exponential enrichment (SELEX), allows rapid identification, from large random sequence pools, of the few oligonucleotide sequences that bind to a desired target molecule with high affinity and specificity. We describe an enzyme-linked sandwich assay that uses a SELEX-derived oligonucleotide. This assay demonstrates that these oligonucleotides can be effective and useful analytical reagents.

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Progressive multifocal leukoencephalopathy results from an opportunistic infection of myelin-producing oligodendrocytes by the glia-specific human papovavirus JC. In this report, evidence is presented that the glial transcription factor Tst-l, a member of the POU-domain family, stimulates transcription of both early and late viral genes. Stimulation was dependent on site-specific binding of Tst-1 to the JC viral regulatory region and on the presence of an intact aminoterminal transactivation domain within Tst-1. Because of its ability to increase the expression of viral large tumor antigen, Tst-1 stimulated viral DNA replication, without participating directly in the replication event. Our results suggest that Tst-1 is one of the determining factors in the glia specificity of JC virus.

For any new class of therapeutics, there are certain types of indications that represent a natural fit. For nucleic acid ligands in general, and aptamers in particular, the eye has historically been an attractive site for therapeutic intervention. In this review, we recount the discovery and early development of three aptamers designated for use in ophthalmology, one approved (Macugen), and two in late-stage development (Fovista and Zimura). Every one of these molecules was originally intended for other indications. Key improvements in technology, specifically with regard to libraries used for in vitro selection and subsequent chemical optimization of aptamers, have played an important role in allowing the identification of development candidates with suitable properties. The lessons learned from the selection of these molecules are valuable for informing us about the many remaining opportunities for aptamer-based therapeutics in ophthalmology as well as for identifying additional indications for which aptamers as a class of therapeutics have distinct advantages.

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Anti-VEGF therapy is a promising new avenue for the treatment of neovascular diseases of the eye, including exudative macular degeneration and diabetic retinopathy. Preclinical data from studies with EYE001 support clinical evaluation of its efficacy in such diseases. This report is the first to describe administration of anti-VEGF therapy in humans for exudative macular degeneration and shows the safety of such therapy for single injections. Further clinical studies are necessary to determine the safety of multiple intravitreal injections of EYE001 and larger studies are needed to prove the efficacy of this novel, potentially therapeutic agent for neovascular AMD.