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Development of the anti-VEGF aptamer to a therapeutic agent for clinical ophthalmology

Authors Cleber A Trujillo, Arthur A Nery, Janaí­na M Alves, Antonio H Martins, Henning Ulrich

Published 15 February 2008 Volume 2007:1(4) Pages 393—402

Cleber A Trujillo1, Arthur A Nery1, Janaína M Alves2, Antonio H Martins1, Henning Ulrich1

1Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil; 2Departamento de Neurologia Experimental, Universidade Federal de São Paulo, São Paulo, Brazil

Abstract: Age-related macular degeneration (AMD) is the main cause of loss of sight in the world and is characterized by neovascularization of the macula. The factors producing choroidal vascularization involve various growth factors, including the vascular endothelial growth factor (VEGF165). In this context, the systematic evolution of ligands by exponential enrichment (SELEX) became a tool for developing new therapeutic agents for AMD treatment. The SELEX is a combinatorial oligonucleotide library-based in vitro selection approach in which DNA or RNA molecules (aptamers) are identified by their ability to bind their targets with high affinity and specificity. Recently, the use of the SELEX technique was extended to isolate oligonucleotide ligands for a wide range of proteins of clinical importance. For instance, Pegaptanib sodium, a 28-nucleotide polyethylene glycol RNA aptamer that selectively binds to VEGF165 and inhibits angiogenesis, was approved by the Food and Drug Administration for the treatment of wet AMD, thereby providing significant benefits to a great number of patients with minimal adverse effects.

Keyword: anti-VEGF aptamer, pegaptanib, age-related macular degeneration

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