Ectopic Gene Expression to Restore the Ascorbate Biosynthesis Pathway in Vertebrates Lacking Functional Gulo
Bibliographic record
Abstract
Background: Vitamin C (VC) deficiency is due to loss of the gene coding for ι-gulono-γ-lactone oxidase (Gulo).VC deficiency is an excellent candidate for therapeutic intervention by ectopic gene expression because a single gene mutation is responsible for the condition and, it is known, a priori, that supplementation effectively rescues the deficiency (at least with respect to the development of scurvy).There are several strategies to ectopically express exogenous genes or silence endogenous genes including viruses and nucleic acids, to ensure that the protein products encoded by exogenous genes are present in the cell, or those encoded by endogenous genes to be silenced are absent.Objective: We review strategies to restore ascorbate biosynthesis in vertebrates.We will discuss the physiology of vitamin C and evaluate the potential of the different methods for the restoration of Gulo expression, and subsequently the endogenous production of VC.Methods: Studies that have targeted manipulation of vitamin C synthesis in vertebrates, particularly the mouse model, over the last 20 years were examined.Results: Vectors of ectopic gene expression were identified as nucleic acids such as linear and plasmid DNA, mRNA, as well as viruses such as adenoviruses and lentiviruses.Direct enzyme replacement was identified as another method of Gulo expression.Conclusion: Ectopic gene expression can be used to rescue metabolic deficiency in VC synthesis using several different modes of delivery.New technologies that directly modify genomes (e.g.CRISPR) that have not yet been applied to this physiological deficiency may allow new investigations into VC physiology.
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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 | 0.001 | 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".