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Record W2921074928 · doi:10.1038/s41598-018-36910-2

Delivery of mRNA to platelets using lipid nanoparticles

2019· article· en· W2921074928 on OpenAlexafffund
Stefanie K. Novakowski, Keran Jiang, Gyan Prakash, Christian J. Kastrup

Bibliographic record

VenueScientific Reports · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsCanada's Michael Smith Genome Sciences CentreUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchCentre for Blood Research, University of British ColumbiaMichael Smith Health Research BCGovernment of CanadaCanada Foundation for InnovationCanadian Blood Services
KeywordsPlateletMessenger RNANanoparticleBioinformaticsChemistryMedicineInternal medicineBiologyBiochemistryNanotechnologyGeneMaterials science

Abstract

fetched live from OpenAlex

Platelets are natural delivery vehicles within the blood, carrying and releasing their contents at sites of vasculature damage. Investigating the biology of platelets, and modifying them for new therapeutic uses, is limited by a lack of methods for efficiently transfecting these cells. The ability of four different classes of lipid nanoparticles (LNPs) to deliver mRNA to platelets was compared using confocal microscopy, flow cytometry and quantitative PCR. The amount of mRNA delivered, mechanism of uptake, and extent of platelet activation depended on the LNP formulation and platelet storage conditions. Cationic LNPs (cLNPs) delivered mRNA to the largest percentage of platelets but induced platelet activation. Ionizable cationic LNPs (icLNPs) delivered mRNA to fewer platelets and did not induce activation. Furthermore, mRNA delivered using icLNPs and cLNPs was stable in resting platelets and was released in platelet microparticles under specific conditions. The results demonstrate that mRNA can be delivered to platelets using cLNPs and icLNPs without impairing platelet aggregation or spreading. Optimizing the LNP formulations used here may lead to a transfection agent for platelets that allows for de novo synthesis of exogenous proteins in the future.

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 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: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score0.342

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 head0.014
GPT teacher head0.248
Teacher spread0.234 · 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 teacher head, 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

Citations42
Published2019
Admission routes2
Has abstractyes

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