Sequence-Controlled Spherical Nucleic Acids: Gene Silencing, Encapsulation, and Cellular Uptake
Bibliographic record
Abstract
Antisense oligonucleotides (ASOs) can predictably alter RNA processing and control protein expression; however, challenges in the delivery of these therapeutics to specific tissues, poor cellular uptake, and endosomal escape have impeded progress in translating these agents into the clinic. Spherical nucleic acids (SNAs) are nanoparticles with a DNA external shell and a hydrophobic core that arise from the self-assembly of ASO strands conjugated to hydrophobic polymers. SNAs have recently shown significant promise as vehicles for improving the efficacy of ASO cellular uptake and gene silencing. However, to date, no studies have investigated the effect of the hydrophobic polymer sequence on the biological properties of SNAs. In this study, we created a library of ASO conjugates by covalently attaching polymers with linear or branched [dodecanediol phosphate] units and systematically varying polymer sequence and composition. We show that these parameters can significantly impact encapsulation efficiency, gene silencing activity, SNA stability, and cellular uptake, thus outlining optimized polymer architectures for gene silencing.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".