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Record W3194583703 · doi:10.33774/chemrxiv-2021-d3dr8

ZIF-C as non-viral delivery system for CRISPR/Cas9 mediated hTERT knockdown in cancer cells

2021· preprint· en· W3194583703 on OpenAlexfundno aff
Suneela Pyreddy, Arpita Poddar, Francesco Carraro, Shakil Ahmed Polash, Chaitali Dekiwadia, Zeyad Nasa, Srinivasa Reddy Telukutla, Paolo Falcaro, Ravi Shukla

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced biosensing and bioanalysis techniques
Canadian institutionsnot available
FundersRMIT UniversityAustralian GovernmentDavid and Elaine Potter FoundationOntario Ministry of Natural Resources and Forestry
KeywordsCRISPRTelomerase reverse transcriptaseTelomeraseCas9Cancer cellCancer researchGene knockdownCarcinogenesisBiologyRibonucleoproteinCancerChemistryGeneRNAGenetics

Abstract

fetched live from OpenAlex

Telomerase, a ribonucleoprotein coded by the hTERT gene, plays an important role in cellular immortalization and carcinogenesis. hTERT is a suitable target for cancer therapeutics as its activity is highly upregulated in 85-90% of cancer cells but absent in normal somatic cells. Here, we target the hTERT gene at the DNA level by applying the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology encapsulated in a recently discovered Metal-Organic Framework (MOF). We show that the MOF subtype ‘ZIF-C’ can efficiently load the hTERT targeting CRISPR system (CrhTERT@ZIF-C) and protect it from enzymatic degradation. The CrhTERT@ZIF-C is endocytosed by cancer cells and successfully disrupts the hTERT gene. The resultant inhibition of hTERT decreases cellular proliferation and causes apoptotic cancer cell death. Furthermore, hTERT knockdown shows a significant reduction in tumor metastasis and alters protein expression. Thus, our results conclusively establish ZIF-C based targeting of hTERT as a highly promising and novel approach for gene therapy in cancer.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.010
GPT teacher head0.295
Teacher spread0.284 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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

Citations1
Published2021
Admission routes1
Has abstractyes

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