Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease

Abstract

Aptamers are oligonucleotide ligands that are selected for high-affinity binding to molecular targets. Pegaptanib sodium (Macugen; Eyetech Pharmaceuticals/Pfizer) is an RNA aptamer directed against vascular endothelial growth factor (VEGF)-165, the VEGF isoform primarily responsible for pathological ocular neovascularization and vascular permeability. After nearly a decade of preclinical development to optimize and characterize its biological effects, pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration. Pegaptanib therefore has the notable distinction of being the first aptamer therapeutic approved for use in humans, paving the way for future aptamer applications.

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

“…69 An VEGF-specific aptamer became the first drug of this kind approved for human therapy to treat age-related macular degeneration. 119 First in vivo modulation of immune responses by aptamers was described for murine CTLA-4, which enhanced tumor immunity. Bivalent and multivalent configurations of other immunomodulatory aptamers binding to 4-1BB or OX40 costimulated T-cell activation in vitro and promoted tumor rejection in vivo.…”

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

“…A post-SELEX approach has been used during the development of the first aptamer drug Macugen Ò (Pegaptanib). 3 Pegaptanib is a human vascular endothelial growth factor (VEGF)-binding RNA aptamer containing 2 0 -F pyrimidine and 2 0 -OMe purine nucleotides. While the aptamer origins from a 2 0 -F pyrimidine-containing library via conventional SELEX, the 2 0 -OMe modifications were introduced post-SELEX by substituting purines to enhance nuclease resistance and serum stability.…”

“…1,2 In 2004, vascular endothelial growth factor (VEGF) targeting RNA aptamer (Mucagen or Pegaptanib sodium) was approved by the Food and Drug Administration (FDA) for age related macular degeneration. 3 Aptamers are typically generated from a large oligonucleotide pool (»10 15 members) via an in vitro reiterative combinatorial selection process called Systematic Evolution of Ligands by EXponential enrichments (SELEX, Fig. 1).…”

Aptamer-based therapeutics and their potential in radiopharmaceutical design

“…Furthermore, the first aptamer has recently successfully reached the pharmaceutical market. This is an anti-VEGF aptamer for the treatment of macular degenerative disease that exerts its action by attacking the neo-vascularization characteristic of this disease, under the name of Macugen (Eyetech/Pfizer) (Ng et al, 2006;Kourlas and Schiller, 2006).…”