Trujillo Cleber A, Nery Arthur A, Alves Janaína M, Martins Antonio H, Ulrich Henning
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Clin Ophthalmol. 2007 Dec;1(4):393-402.
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 (VEGF(165)). 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 VEGF(165) 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.
年龄相关性黄斑变性（AMD）是全球视力丧失的主要原因，其特征是黄斑新生血管形成。导致脉络膜血管化的因素涉及多种生长因子，包括血管内皮生长因子（VEGF(165)）。在这种情况下，指数富集配体系统进化技术（SELEX）成为开发用于治疗AMD的新型治疗药物的一种工具。SELEX是一种基于组合寡核苷酸文库的体外筛选方法，其中DNA或RNA分子（适配体）通过其以高亲和力和特异性结合靶标的能力来鉴定。最近，SELEX技术的应用扩展到分离针对多种具有临床重要性的蛋白质的寡核苷酸配体。例如，聚乙二醇化核酸适体钠，一种28个核苷酸的聚乙二醇化RNA适配体，可选择性结合VEGF(165)并抑制血管生成，已被美国食品药品监督管理局批准用于治疗湿性AMD，从而为大量患者带来显著益处且副作用极小。
