A Comparative Evaluation of Disulfide-Linked and Hydrophobically-Modified PEI for Plasmid Delivery
Bibliographic record
Abstract
Non-viral gene therapy has become an important approach for treatment of hereditary and acquired diseases as a result of better understanding of molecular mechanisms involved in disease development. To design more effective gene carriers, plasmid DNA (pDNA) delivery to 293T cells was investigated by using two types of polymeric carriers; polymer constructed with disulfide (-S-S-) linkages and polymers modified with hydrophobic moieties. The base polymer used for this study was 2-kDa poly(ethylene imine) (PEI2), a relatively cell-compatible but ineffective gene carrier. The -S-S- linking was achieved via Michael addition reaction using cystamine bisacrylamide (CBA), whereas hydrophobic modification by N-acylation of PEI2 amines with palmitoyl chloride (PA). The cytotoxicity of the polymers was found to be lower than that of the 25-kDa branched PEI, but both types of modifications increased the toxicity of PEI2 to some extent. The polymers were able to form polyplexes with pDNA with variable hydrodynamic sizes (130-600 nm) and ζ-potential (3.6-20.9 mV). Based on the expression of the reporter gene Enhanced Green Fluorescent Protein (EGFP), disulfide linking significantly increased the efficiency of native PEI2, which was not effective on its own. The PA-modified PEI2 was also effective for gene delivery, but disulfide linkage of this polymer did not increase its efficiency any further. Our results showed that hydrophobic modification of 2-kDa PEI significantly improved its transfection efficiency but improvements in transfection efficiency as a result of disulfide linking was dependent on the nature of the polymeric building blocks.
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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".