Ministring DNA (msDNA): a novel linear covalently-closed DNA with enhanced stability for gene and cell therapy applications
Bibliographic record
Abstract
The quality and fidelity of DNA vectors used in genetic medicine and gene therapy either as starting material for manufacturing or as therapeutic ingredients play a critical role in determining ultimate clinical success. Ministring DNA (msDNA), is a novel minivector that is a linear covalently-closed (LCC) double-stranded DNA molecule devoid of immunogenic bacterial sequences (e.g., origin of replication, antibiotic resistant cassette). Similar to traditional plasmids, msDNA is manufactured in vivo in E. coli and therefore benefits from the scalability of E. coli -based systems and the ~ 1000-fold enhanced fidelity conferred by the mismatch repair (MMR) mechanism. In this paper, we address the improved stability of msDNA. We show that due to the torsion-free structure, msDNA is more stable to chemical and mechanical stress than conventional plasmid DNA. Moreover, we demonstrate that lyophilization can further improve the long-term stability of msDNA, reducing the need for cold chain storage. Therefore, we propose that msDNA can be a new paradigm for genetic medicine by offering genetic material with lower immunogenicity, reduced risk of insertional mutagenesis, and higher fidelity and stability.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".