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Highly efficient non-viral delivery of macromolecules to unactivated human T cells using microfluidic transfection

2024· article· en· W4404167771 on OpenAlexaff
Manreet Chehal, Éric Ouellet, Elinor Binson, Quan Nguyen, Tina Liao, Phillip Chau, Kris Chen, Ulrike Lambertz, Jessie Z. Yu, Scott Loughhead, Bob Dalton, Allen Eaves, Sharon A. Louis, Andy I. Kokaji

Bibliographic record

VenueThe Journal of Immunology · 2024
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsStemcell Technologies
Fundersnot available
KeywordsTransfectionMacromoleculeMicrofluidicsNanotechnologyGene deliveryCell biologyChemistryMaterials scienceBiologyBiochemistryGene

Abstract

fetched live from OpenAlex

Abstract Traditional methods for transfecting unactivated human T cells are limited in their delivery efficiency while maintaining cell viability, phenotype, and function. To address these challenges, we developed the CellPore™ Transfection System. This microfluidic platform creates transient disruptions in the plasma membrane via pressure-induced mechanical deformation, allowing for cytosolic delivery. First, we developed a workflow to optimize delivery pressure to T cells using FITC-dextran. This optimized pressure was used to deliver mRNA for expression of eGFP (91.8%) and mCherry (92.9%), and Cas9 RNP complexes targeting B2M and TRAC, with knockout efficiencies of 74.0% MHC-I and 93.9% TCRαβ, respectively. Importantly, while electroporation of T cells resulted in increased expression of the activation marker CD69 (41.2%) and proinflammatory cytokines (77.7 pg/mL IL-2, 8.8 pg/mL IFNγ), CellPore™-transfected T cells maintained an unactivated phenotype (0.8% CD69+, 0.1 pg/ml IL-2 and 0.2 pg/ml IFNγ) and were capable of downstream activation/expansion via CD3, CD28, and CD2 cross-linking. Using this optimized workflow, efficient cytosolic delivery of FITC-dextran to human CD4 (97.4%), CD8 (96.6%) and regulatory (98.3%) T cells was also achieved. The CellPore™ Transfection System enables robust and efficient delivery of cargo to T cells without impacting cell function in a simple workflow that can easily be integrated into research protocols.

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 communication0.0010.000
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 head0.018
GPT teacher head0.301
Teacher spread0.282 · 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
Published2024
Admission routes1
Has abstractyes

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