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Record W7114789073 · doi:10.1021/acs.oprd.5c00346

Fully Liquid Phase Oligonucleotide Synthesis

2025· article· en· W7114789073 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.

Bibliographic record

VenueOrganic Process Research & Development · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA and Nucleic Acid Chemistry
Canadian institutionsVictoria Park
FundersInnovate UKNovartis PharmaAlnylam PharmaceuticalsAstraZeneca
KeywordsOligonucleotideReagentCleavage (geology)MembranePhase (matter)Oligonucleotide synthesisLiquid phaseSolid-phase synthesis

Abstract

fetched live from OpenAlex

Representative oligonucleotides (oligos), a 21-mer siRNA strand and a 16-mer ASO-like gapmer, were synthesized by Nanostar Sieving, a membrane-assisted liquid phase oligo synthesis (LPOS) method, at a 10 mmol scale and 20 mM concentration in a single solvent. This process is the first total LPOS beyond 10-mer, i.e., the reagents and intermediates remain in the liquid phase from the very first reaction to isolation. At all times during the synthesis of the full-length product, the concentration of oligos within the Nanostar-10 reactor remained roughly constant. Both sequences were synthesized four times, twice using membrane sheets clamped flat in circular cells and twice using scalable spiral wound modules. Cleavage and deprotection continued to maintain the oligo in the liquid phase until the final lyophilization, when yields were calculated from the optical density, adjusting for chromatographic and mass spectral purity. Synthetic process mass intensities approaching those of solid phase oligo synthesis (SPOS) were achieved.

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)0.001
metaresearch head score (Gemma)0.001
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: Empirical · Consensus signal: Empirical
Teacher disagreement score0.096
Threshold uncertainty score0.787

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 science0.0010.000
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 head0.017
GPT teacher head0.354
Teacher spread0.337 · 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