SIRNA Delivery Mediated By Inulin Based Polycations
Bibliographic record
Abstract
RNA interference is a technique to induce specific gene silencing, mediated by siRNAs, double stranded RNA molecules (19-27 bp) that induce specific mRNA degradation in the cytoplasm [1].Despite the immense therapeutic potentiality, siRNAs suffer of poor stability in vivo and almost zero uptake by cells due to high molecular weight, hydrophilicity and the presence of negative charges [2].Polyplexes, colloidal systems originated from the electrostatic interaction between negative nucleic acids and positive charged polymers, emerged as one of the most versatile systems for nucleic acid delivery Our current research focuses on the generation of libraries of graft semisynthetic polycations with multiple architectures and analogue composition, starting from Inulin (INU), a natural polysaccharide, to explore how the structure of the carrier influences the delivery process.Inulin is constituted by a PEG backbone from which one fructose ring per repeating unit is hanging.It has already been investigated as scaffold for the design of siRNA vectors [3][4] and as PEG alternative in amphiphilic derivatives for nanocostruction [5].Contrarily to PEG, INU has the advantage of being natural, non-immunogenic and functionalizable along its entire length, allowing the modulation of composition and architecture in a smooth way.In this contribution we present the first derivatives of the serie INU-PEI: Inulin-g-branched polyethyleneimine (INU-bPEI) and its amphiphilic analogue INU-bPEI-PLA.Derivatives with two different derivatization degree in PEI were tested to prepare copolymer/siRNA polyplexes by interpolyelectrolytic interactions.Agarose gel retardation assay showed that this new copolymers were able to stop the electrophoretic run of siRNA.Complexes were characterized by DLS studies and by stability studies in the presence of albumin.Our investigation showed the ability of this systems to resist to the anionic exchange.In addition, haemocompatibility of polyplexes was demonstrated.This early results encourage us to continue in this study to obtain efficient inulin based siRNA delivery systems.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".