Circulating hematopoietic stem cells serve as novel targets for in utero gene therapy
Bibliographic record
Abstract
ABSTRACT In utero gene therapy has been proposed as a method for permanent correction of somatic disorders that affect the hematopoietic system before disease initiation (1, 2). However, clinical trials using transplantation of allogenic fetal liver, bone marrow, or adult stem cells have been unsuccessful, largely due to the failure of sustained hematopoietic reconstitution in fetal recipients (3). Here, we reveal that retroviral transduction of unique repopulating stem cells found in the human fetal circulation is superior to full‐gestation cord blood or adult sources. In contrast to postnatal human stem cells, the fetal circulation is highly enriched for actively cycling blood stem cells, thereby forming the basis for enhanced transduction. Our findings indicate that active, transducible hematopoietic reconstituting cells are present in the circulation of the human fetus and that they represent novel target cells for future in utero gene therapy trials using autologous transplantation.
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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 | 0.001 | 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".