Summary

• Aptamers are RNA or DNA oligonucleotides that are selected through systematic evolution to bind to proteins with both affinity and specificity.
• Aptamers offer the specificity and affinity advantages of antibodies in a relatively small, chemically synthesized molecule free from cell-culture-derived contaminants. They are also essentially non-immunogenic.
• In contrast to other oligonucleotide agents, such as antisense oligonucleotides, aptamers can act on extracellular targets.
• Vascular endothelial growth factor (VEGF) was selected as a target for aptamer development owing to its key role in pathological angiogenesis, for example, in ocular neovascular diseases such as age-related macular degeneration (AMD) and diabetic macular oedema.
• After the selection of anti-VEGF aptamers that blocked the actions of VEGF in vitro, further optimization of the pharmacokinetic properties, for example by using 2'-F substitutions, resulted in the pegylated aptamer pegaptanib, which was chosen for clinical development.
• Pegaptanib, administered by intravitreous injection, was tested in clinical trials in patients with neovascular AMD, and on the basis of its ability to reduce vision loss, was approved by the US FDA in December 2004.