Synthesis of Antisense Oligonucleotides Conjugated to a Multivalent Carbohydrate Cluster for Cellular Targeting
Bibliographic record
Abstract
Carrier-mediated delivery holds great promise for significantly improving the cellular uptake and therefore the therapeutic efficacy of antisense oligonucleotides in vivo. A multivalent carbohydrate recognition motif for the asialoglycoprotein receptor has been designed for tissue- and cell-specific delivery of antisense drugs to parenchymal liver cells. To combine low molecular weight with high receptor affinity, the synthetic ligand contains three galactosyl residues attached to a cholane scaffold via epsilon-aminocapramide linkers. Three-dimensional structural calculations indicate that this unique design provides proper spacing and orientation of the three galactosyl residues to accomplish high affinity binding to the receptor. Covalent conjugation of the bulky carbohydrate cluster to oligonucleotides has been achieved by solid-phase synthesis using low-loaded macroporous resins and optimized synthesis protocols.
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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 | 0.001 |
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".