Cellular Uptake and Metabolism of DNA Frayed Wires
Bibliographic record
Abstract
DNA frayed wires are a novel, multistranded form of DNA that arises from interactions between single-stranded oligodeoxyribonucleotides with the general sequence d(N(x)G(y)) or d(G(y)N(x)), where y > 10 and x > 5. Frayed wires exhibit greater stability with respect to thermal and chemical denaturation than single- or double-stranded DNA molecules and, thus, may have potential usefulness for DNA drug delivery. However, the stability and uptake of frayed wires have not been investigated in biological systems. Our objective was to examine the cellular uptake and stability of frayed wires in cultured hepatic cells. In these studies, the parent oligonucleotide d(A(15)G(15)) was used to form DNA frayed wires (DNA(FW)) while a random 30-mer oligonucleotide was used as the control nonaggregated DNA (DNA(SS)). Uptake and metabolism studies of DNA(FW) were performed in cultured human hepatoma, HepG2 cells and compared to DNA(SS). Our results indicate that DNA(FW) are not cytotoxic and that their intracellular uptake in HepG2 cells is 2-3.5-fold greater than that of DNA(SS) within the first 2 h (p < 0.05). Similarly, nuclear localization of DNA(FW) is 10-13-fold higher than that of DNA(SS) (p < 0.05). As both internalized and extracellular DNA(FW) appear to be more stable in vitro than DNA(SS), the enhanced uptake may be due to either increased stability or enhanced intracellular transport. These studies also indicate that uptake of DNA(FW) likely occurs via active processes such as receptor-mediated endocytosis similar to mechanisms which have been proposed for DNA(SS). The internalization pathways of DNA(FW) may differ somewhat from that of DNA(SS) insofar as chloroquine does not appear to alter DNA(FW) uptake and degradation, as is the case with DNA(SS).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".