Programmable Single-Stranded Circular Antisense Oligonucleotides for Multitarget Gene Therapy
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Oligonucleotide therapeutics, especially antisense oligonucleotides (ASOs), provide promising treatments for various diseases, with combinatorial ASO therapy increasing the efficacy. However, challenges persist in enhancing stability and ensuring precise delivery. Here, we proposed the use of single-stranded circular ASOs (circASOs) for the cosilence of multiple genes, which was demonstrated with universality. Notably, unmodified circASOs achieved a similar silencing efficiency compared to chemically modified ASOs. Multitargeted circASOs were also designed for simultaneous silencing of different genes, showing prolonged and higher gene silencing due to their high biostability. Furthermore, the circASO is compatible with various chemical modifications, which could further enhance the circASO functionality. This programmable circular ASO platform provides a versatile tool for designing multifunctional nucleic acid medicines for gene therapy.
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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