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Record W7000153913

Enzyme-instructed siRNA Release and Functional Self-assembly of Peptide-based Delivery System

2021· dissertation· en· W7000153913 on OpenAlexfundno aff

Bibliographic record

VenueUWSpace (University of Waterloo) · 2021
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsnot available
FundersUniversity of WaterlooMitacs
KeywordsEndosomeTransfectionSmall interfering RNAPeptideEndocytosisRNARNA interferenceLiposomePhosphorylationGene delivery
DOInot available

Abstract

fetched live from OpenAlex

Cell-penetrating peptide (CPP)-based small interfering RNA (siRNA) delivery is one of the approaches with great potential to achieve RNA interference (RNAi) applied in gene therapy. CPP-based siRNA carriers hold many merits, including biodegradability, high transmembrane efficiency, and capability of endosomal escape. Despite considerably high transfection efficiency achieved, there are still many challenges in further improving the CPP-based siRNA delivery systems. This proposal focuses on two of the challenges: (1) the dissociation of negatively charged siRNA from a positively charged peptide; and (2) minimization of cytotoxicity of CPPs while maintaining capacity in endosomal escape. Herein, we propose to utilize enzyme-catalyzed phosphorylation to induce the transfer of negatively charged phosphate groups onto the cationic CPPs formulated with siRNA; the emergent phosphate groups can facilitate the dissociation of siRNAs from the complex due to electrostatic repulsion between the two negatively charged species, the phosphate groups on the peptide and the siRNA. The presence of phosphate groups also alters the balance between repulsive and attractive forces that govern the self-assembly of the peptide, resulting in conformational changes.

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 score0.001
Threshold uncertainty score0.003

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.006
GPT teacher head0.179
Teacher spread0.173 · 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

Citations0
Published2021
Admission routes1
Has abstractyes

Explore more

Same venueUWSpace (University of Waterloo)Same topicRNA Interference and Gene DeliveryFrench-language works237,207