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Record W4312919370 · doi:10.47611/jsr.v11i1.1534

Current Sickle Cell Disease Gene Therapy Treatments: Literature Review

2022· article· en· W4312919370 on OpenAlexaff
Anika Ranadive, Janaksha Linga-Easwaran

Bibliographic record

VenueJournal of Student Research · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversity of TorontoMcMaster University
Fundersnot available
KeywordsGenetic enhancementCRISPRGenome editingDiseaseViral vectorFetal hemoglobinCas9MedicineGeneHaematopoiesisStem cellClinical trialBioinformaticsMutationImmunologyBiologyFetusInternal medicineGeneticsPregnancyRecombinant DNA

Abstract

fetched live from OpenAlex

Sickle cell disease (SCD) consists of haemoglobin-mutation related blood disorders caused by mutations of the HBB gene. Current treatments for SCD are symptom-based or preventive treatments. The only curative treatment for SCD- an allogeneic hematopoietic stem cell transplant- is inaccessible to the majority of SCD patients. The transplant required a donor graft is unavailable for most individuals. Currently, research in gene therapy treatment for SCD attempts to provide long-lasting treatments in two distinct techniques. The first technique is to change the mutation-containing genotype to produce a normal or functional haemoglobin protein. The second technique is to bypass the production of the mutated adult haemoglobin and product fetal haemoglobin instead. This literature review compares three gene-editing methods; Lentiviral Vectors, CRISPR/Cas9, and Base Editors. A review of previously published research papers was conducted and compared over a 2 month period during a summer student research program to determine the progression of each of the three gene-editing methods in the two techniques of SCD gene therapy treatment. While all three were successful in both genotype correction and fetal haemoglobin induction, only the Lentiviral Vector and CRISPR/Cas9 treatments for fetal haemoglobin induction have published data on human trials. However, the Base Editor shows promise in its ability to surpass many issues faced with both viral vectors and CRISPR/Cas9 such as off-target DNA breaks. Progression in SCD gene therapy can provide a treatment option for all affected individuals and can even provide a basis for gene therapy for other blood disorders.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.745
Threshold uncertainty score0.308

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.050
GPT teacher head0.464
Teacher spread0.414 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

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".

Quick stats

Citations2
Published2022
Admission routes1
Has abstractyes

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