Recombinant micro-dysferlins for gene therapy of dysferlinopathies
Bibliographic record
Abstract
Mutations in the dysferlin gene cause limb-girdle muscular dystrophy 2B. Dysferlin has been shown to be required for the calcium-dependent repair of muscle fibers following an induced membrane injury. Adeno-associated viral vectors, which are well suited for gene therapy, cannot accommodate full-length dysferlin. If this approach is to be used, only truncated forms of dysferlin, (micro-dysferlins) can be incorporated in these vectors. We hypothesize that micro-dysferlins, expressed in dysferlin deficient myoblasts, can rescue the calcium dependent repair mechanism. Four micro-dysferlins were generated and successfully expressed in C2C12 myoblasts. Primary myoblast cultures from dysferlin deficient (A/J) and wild-type (C57BL/6) were established and a scrape injury followed by a cell survival assay demonstrated that wild-type primary myoblasts have a calcium-dependent membrane repair system; whereas dysferlin deficient myoblasts do not. Attempts to express micro-dysferlin in dysferlin deficient myoblasts have yielded poor rates of transfection with conventional cationic lipids. As a result the ability of micro-dysferlins to increase cell survival in a calcium dependent manner has not been tested.
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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 | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".