Plant Recombinant Lysosomal Enzymes as Replacement Therapeutics for Lysosomal Storage Diseases
Bibliographic record
Abstract
Lysosomal storage diseases (LSDs) are a broad class of over 70 genetic diseases that are caused by mutations in proteins critical for lysosomal function; collectively these diseases have an estimated prevalence of 1 in 5000 live births. LSDs can be treated by enzyme replacement therapy (ERT) in which the purified recombinant enzyme is delivered intravenously to patients by weekly infusions. Plant-based platforms for ERT drug production are being pursued; these may enable more economical and safe treatments than traditional production platforms. Yet the use of plant platforms poses significant technical challenges – one of which is associated with generating a therapeutically efficacious product. The administered recombinant enzyme must have suitable targeting signals for endocytosis into patient cells and for intracellular delivery to the lysosome. For many enzymes this requires the mannose-6-phosphate (M6P) tag on the replacement protein. Elaboration of this trafficking motif requires post-translational enzymatic machinery that is not present in plant cells. We discuss approaches to effect M6P elaboration onto plant-made recombinant lysosomal hydrolases, as well as emerging alternative modifications for improved biodistribution of ERT.
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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 | 0.000 | 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".