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Record W4405651848 · doi:10.1002/smtd.202401600

Dimeric DNA Aptamers for the Spike Protein of SARS‐CoV‐2 Derived from a Structured Library with Dual Random Domains

2024· article· en· W4405651848 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueSmall Methods · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced biosensing and bioanalysis techniques
Canadian institutionsMcMaster University
FundersNatural Sciences and Engineering Research Council of CanadaMitacs
KeywordsAptamerLinkerDNAComputational biologySystematic evolution of ligands by exponential enrichmentAvidityChemistryTarget proteinIn vitroSELEX Aptamer TechniqueCombinatorial chemistryBiophysicsBiologyMolecular biologyComputer scienceBiochemistryGeneticsRNAGeneAntibody

Abstract

fetched live from OpenAlex

Abstract Multimeric aptamer strategies are often adopted to improve the binding affinity of an aptamer toward its target molecules. In most cases, multimeric aptamers are constructed by connecting pre‐identified monomeric aptamers derived from in vitro selection. Although multimerization provides an added benefit of enhanced binding avidity, the characterization of different aptamer pairings adds more steps to an already lengthy procedure. Therefore, an aptamer engineering strategy that directly selects for multimeric aptamers is highly desirable. Here, an in vitro selection strategy is reported on using a pre‐structured DNA library that forms dimeric aptamers. Rather than using a library containing a single random region, which is nearly ubiquitous in existing aptamer selections, the library contains two random regions separated by a flexible poly‐thymidine linker. Following sixteen rounds of selection against the SARS‐CoV‐2 spike protein, a relevant model target protein due to the COVID‐19 pandemic, the top aptamers displayed superb affinity with K D values as low as 150 pM. Further analysis reveals that each random region functions as a distinct binding moiety and works together to achieve higher affinity. The demonstrated strategy provides an accelerated method to obtain high‐affinity aptamers, which may prove useful in future aptamer diagnostic and therapeutic applications.

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.

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)0.000
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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.083
Threshold uncertainty score0.464

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.022
GPT teacher head0.326
Teacher spread0.304 · 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