DISTRIBUTION AND EXPRESSION OF TRANSGENE GREEN FLUORESCENT PROTEIN IN MICE SURVIVING UP TO 4 WEEKS FOLLOWING IN UTERO GENE THERAPY.
Bibliographic record
Abstract
Gene replacement offers a potential cure for degenerative disorders caused by a single gene deletion or mutation. Diagnoses of monogenic disorders in the fetus enable prenatal gene replacement, which may be beneficial from the perspectives of host inflammatory/immune response, efficacy, and disease prevention. Purpose The purpose of our study was to evaluate the distribution and expression of reporter gene green fluorescent protein (GFP) in the tissues of mice surviving up to 1 month following in utero gene therapy. Methods Used Vesicular stomatitis virus-G (VSV-G) pseudotyped lentiviral (LV) vector containing GFP was prepared via triple plasmid cotransfection. Time-mated CD-1 mice underwent individual amniotic sac injection with either 1 × 106 LV particles or saline (controls) on gestational day 16 (term = 21 days) and were allowed to undergo spontaneous parturition. Pups were sacrificed on postnatal days 0, 7, 21, and 28, and neonatal and maternal tissues were analyzed for GFP transgene (by DNA polymerase chain reaction; PCR) and transgene expression by quantitative reverse transcriptase (QRT) PCR and immunohistochemistry (IHC). Summary of Results We observed selective transduction of neonatal tissues (trachea, lung, liver, heart, kidney, spleen, intestine, skeletal muscle) in pups undergoing in utero transfection with LV-GFP. Maternal tissues did not contain transgene despite exposure during amniotic injection. Although the number of pups analyzed at each postnatal time point was small, we observed variable persistence of GFP expression that appeared to be tissue specific (with persistent expression noted in the intestine of 4-week-old pups). Conclusions Neonatal tissue transfection occurs in a variety of tissues following amniotic injection with LV-GFP in this murine model of in utero gene therapy. Transgene persistence and expression patterns observed over the first 4 weeks of life may reflect tissue-specific genomic insertion of transgene that favors persistent transcription in select tissues.
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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 | 0.003 | 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".