A Short DNA Aptamer That Recognizes TNFα and Blocks Its Activity <i>in Vitro</i>
Why this work is in the frame
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Bibliographic record
Abstract
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.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it