Anti-TNF alpha Aptamer [TNFa] (Biotin) (A320906)

Tumor necrosis factor-alpha (TNFa) is a pivotal component of the cytokine network linked to inflammatory diseases. Protein-based, TNFa inhibitors have proven to be clinically valuable. Here, we report the identification of short, single-stranded DNA aptamers that bind specifically to human TNFa. One such 25-base long aptamer, termed VR11, was shown to inhibit TNFa signaling as measured using NF-?B luciferase reporter assays. This aptamer bound specifically to TNFa with a dissociation constant of 7.0 ± 2.1 nM as measured by surface plasmon resonance (SPR) and showed no binding to TNFß. Aptamer VR11 was also able to prevent TNFa-induced apoptosis as well as reduce nitric oxide (NO) production in cultured cells for up to 24 h. As well, VR11, which contains a GC rich region, did not raise an immune response when injected intraperitoneally into C57BL/6 mice when compared to a CpG oligodeoxynucleotide (ODN) control, a known TLR9 ligand. These studies suggest that VR11 may represent a simpler, synthetic scaffold than antibodies or protein domains upon which to derive nonimmunogenic oligonucleotide-based inhibitors of TNFa.