1 research outputs found
A Short DNA Aptamer That Recognizes TNFα and Blocks Its Activity <i>in Vitro</i>
Tumor necrosis factor-alpha (TNFα) is a pivotal
component
of the cytokine network linked to inflammatory diseases. Protein-based,
TNFα inhibitors have proven to be clinically valuable. Here,
we report the identification of short, single-stranded DNA aptamers
that bind specifically to human TNFα. One such 25-base long
aptamer, termed VR11, was shown to inhibit TNFα signaling as
measured using NF-κB luciferase reporter assays. This aptamer
bound specifically to TNFα with a dissociation constant of 7.0 ±
2.1 nM as measured by surface plasmon resonance (SPR) and showed no
binding to TNFβ. Aptamer VR11 was also able to prevent TNFα-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
TNFα