VEGFAAptamer

VEGFAAptamer refers to a class of nucleic acid aptamers that bind vascular endothelial growth factor A (VEGF-A). These short, single-stranded DNA or RNA molecules are selected for high affinity and specificity to VEGF-A using the SELEX process and are frequently modified to improve nuclease resistance and pharmacokinetic properties. By occupying VEGF-A's receptor-binding interface, VEGFAAptamers prevent signaling through VEGF receptors (primarily VEGFR-1 and VEGFR-2) and thereby inhibit angiogenesis in pathological contexts such as cancer and retinal neovascular diseases.

Pegaptanib sodium (Macugen) is the best-known VEGFAAptamer. It is an RNA aptamer that binds VEGF-A165 with high affinity and was approved by the U.S. FDA in 2004 for the treatment of neovascular age-related macular degeneration. Delivered by intravitreal injection, pegaptanib blocks VEGF-A–VEGFR interactions and can slow vision loss in some patients. Its use has declined with the advent of more potent anti-VEGF antibodies and fusion proteins, but it remains a landmark example of aptamer therapy.

Beyond pegaptanib, researchers have developed additional VEGF-binding aptamers of RNA and DNA chemistries and explored chemical modifications such as 2'-fluoro or 2'-O-methyl substitutions and PEGylation to extend half-life. Some candidates have entered preclinical studies or early-stage clinical trials, exploring ocular and systemic indications. Challenges for VEGFAAptamers include achieving sufficient tissue exposure, long-term stability, and delivery, particularly for retinal applications that require local administration.

Overall, VEGFAAptamers illustrate the therapeutic potential of aptamer-based VEGF inhibition, offering a non-protein alternative with distinct pharmacology and immunogenicity profiles. They continue to inform development of next-generation anti-angiogenic agents and diagnostic tools for VEGF-related diseases.