Aliphatic Lipid Substitution on 2 kDa Polyethylenimine Improves Plasmid Delivery and Transgene Expression
Bibliographic record
Abstract
This study was conducted in order to develop amphiphilic, low molecular weight polymeric carriers for nonviral gene delivery. Caprylic, myristic, palmitic, stearic, oleic and linoleic acids were grafted onto the 2 kDa polyethylenimine (PEI) and properties critical for gene delivery were investigated using 293T and bone marrow stromal cells. The extent of lipid substitution on the polymers was controlled by the lipid:PEI feed ratio during the synthesis. The toxicity of the native and lipid-substituted 2 kDa PEI was relatively lower than the 25 kDa PEI, although lipid substitution generally increased the toxicity of the polymers in vitro. Lipid substitution reduced the ability of the polymers to complex DNA, as well as the stability of final complexes, as measured by heparin-induced dissociation. Once fully complexed to a plasmid DNA, however, the lipid-substituted polymers increased the plasmid DNA delivery to the cells. In 293T cells, the lipid-substituted polymers displayed a transfection ability that was equivalent to highly effective 25 kDa PEI, but without the toxic effect associated with the latter polymer. Among the lipids explored, no particular lipid emerged as the ideal substituent for transgene expression, although linoleic acid appeared to be superior to other lipid substituents. No correlation was evident between the level of substitution and DNA delivery efficiency of the polymers, and as little as 1 lipid substitution per PEI was effective in transforming the ineffective 2 kDa PEI into an effective carrier. The current structure-function studies are providing important clues about the properties critical for gene delivery and providing carriers effective for nonviral plasmid delivery.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".