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Record W4415461494 · doi:10.1021/acs.jmedchem.5c01648

Exploring Chemically Modified Short Activating RNAs to Increase Stability against Nucleases and Enhance Gene Activation

2025· article· en· W4415461494 on OpenAlexafffund
Jean‐Paul Desaulniers, Matthew L. Hammill, Ifrodet Giorgees, Virginia Wing-Nam Chiu, Hannah M. Pendergraff, Sara Aguti, Jon Voutila, Nagy Habib, Yulia Lomonosova, Troels Koch

Bibliographic record

VenueJournal of Medicinal Chemistry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsOntario Tech University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsNucleaseNucleic acidArgonauteGene silencingRNAGene expressionGeneRNA interferenceSmall interfering RNA

Abstract

fetched live from OpenAlex

Short activating RNAs (saRNAs) are short duplex RNAs that activate genes in the nucleus of the cell. This induces gene activation, or RNA activation (RNAa), which upregulates gene expression. This activation is in direct contrast to short interfering RNAs (siRNAs), which downregulate gene expression through the activation of Argonaute 2 within the RNA-induced silencing complex (RISC). siRNA chemical modifications such as 2'-O-Me, 2'-F, locked nucleic acids (LNA), unlocked nucleic acids (UNA), and backbone modifications such as phosphorothioate (PS) have been well documented and studied. In this study, a library of chemically modified saRNAs was synthesized and evaluated for their ability to activate gene expression. We have identified that a thermally destabilizing abasic carbon-based linker within the central region of the sense strand, in conjunction with an affinity-enhancing nucleoside, LNA, on the antisense strand, offers optimal duplex melting temperature, nuclease stability, and enhanced gene activation.

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 head0.039
GPT teacher head0.283
Teacher spread0.244 · 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
Published2025
Admission routes2
Has abstractyes

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