160. Additive Nanocomplexes of Cationic Lipopolymers for Improved Non-Viral Gene Delivery to Mesenchymal Stem Cells
Bibliographic record
Abstract
It has been a challenging task to transform MSC into therapeutically useful cells. Most studies were conducted with viral vectors, despite serious concerns on immunogenicity of the viral approach [1]. Cationic polymers display greater chemical diversity than lipids and accommodate versatile chemical schemes to incorporate functional moieties for better transfection[2]. Herein, we have developed a ternary nano-formulation for gene delivery to umbilical cord blood MSC and bone marrow MSC by using lipid-modified small (1.2 kDa) molecular weight polyethylenimine (PEI1.2) (Figure 1). Linoleic acid (LA) was end-capped with carboxyl functionality by coupling with mercaptopropionic acid through thio-ester linkage, and then grafted onto PEI1.2 via N-acylation. Structural functionalities of modified LA (tLA) and thio-ester LA grafted PEI1.2 (PEI-tLA) were analyzed through 1H-NMR spectroscopy and TNBS assay. To create polymer/pDNA complexes that more conducive for dissociation, polyanionic additive (hyaluronic acid, HA) was incorporated along with pDNA to PEI-tLA complexes. The binding capacity of the polymers and unpacking of resultant complexes was elucidated by an agarose gel retardation assay. PEI-tLA displayed a significantly lower (up to 6-fold) pDNA binding capability and a higher dissociation propensity. The dissociation ability of PEI-tLA/pDNA complexes was further enhanced by HA incorporation. The effect of HA was negligible in hydrodynamic size of the complexes but it significantly decreased surface charge which is essential to minimize cellular toxicity of cationic polymers [3]. PEI-tLAs displayed better compatibility to MSC compared to commercial targeting agents and conventional PEI-LA polymers. In vitro transfection efficiency of PEI-tLAs in MSC was substantially higher than positive control. The higher gene expression was the consequence of better cellular uptake, observed through confocal microscopy and flowcytometric study. Transfection efficiency of PEI-tLA was further increased using ternary complexes with HA, which was comparable to or higher than Lipofectamine™ 2000 and PEI25. The synergism between polyanionic additive (e.g. HA) and electronegative functionality (e.g. thio-ester, -S-CO-) of aliphatic lipids can generates a supersensitive nano-formulation which could be a potential carrier for the modification of primary cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".