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Record W4404354994 · doi:10.26434/chemrxiv-2024-l9fn9

The transfection potency of lipid nanoparticles containing mRNA depends on relative loading levels

2024· preprint· en· W4404354994 on OpenAlexaff
Suiyang Liao, Shuangyu Wang, Abishek Wadhwa, Alex Birkenshaw, Kevin Fox, Miffy H. Y. Cheng, Irafasha C. Credo, Armando Alcázar Magaña, Nuthan Vikas Bathula, Cheryl Ho, Melody M. Cheng, Leonard J. Foster, Kenneth W. Harder, Colin J.D. Ross, Pieter R. Cullis, Anna K. Blakney

Bibliographic record

VenueChemRxiv · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsPotencyTransfectionMessenger RNANanoparticleChemistryBiophysicsNanotechnologyBiochemistryIn vitroMaterials scienceBiologyGene

Abstract

fetched live from OpenAlex

When formulating mRNA into lipid nanoparticles (LNP), various copy numbers of mRNA are encapsulated, leading to a distribution of mRNA loading levels within LNPs. It is unclear if the mRNA loading level affects the functional delivery of the message. Here we show that depending on the mRNA loading level, LNPs exhibit distinct mass densities and can be fractionated via ultracentrifugation. Upon fractionation, we investigated if mRNA loading levels influence LNP sizing, lipid composition and morphology. We further conducted in vitro and in vivo functional delivery of mRNA and found that the LNP fraction with highest mRNA loading levels were the least transfection competent.

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)0.001
metaresearch head score (Gemma)0.001
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
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.026
GPT teacher head0.273
Teacher spread0.247 · 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
Published2024
Admission routes1
Has abstractyes

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