Direct Conjugation of Gallium‐(III)‐Corroles to Short Interfering RNA(siRNA) Providing Real‐Time siRNA Imaging and Gene Silencing
Bibliographic record
Abstract
Abstract Discovering new modifications for oligonucleotide therapeutics is essential for expanding its application to new targets and diseases. In this project, we focus on conjugating metaled ligands to short interfering RNAs (siRNAs) to investigate robust and simple conjugation methods for adding new properties such as real‐time imaging to the siRNA. Here we report the chemical synthesis of novel Ga‐(III)‐corroles for their direct conjugation to siRNAs. Ga‐(III)‐corrole‐siRNAs showed promising results when evaluated for gene silencing and live cell imaging. The knockdown activity of the firefly luciferase reporter gene was measured to evaluate gene silencing activity. Gene silencing studies from two 5’‐Ga‐(III)‐labeled‐siRNAs exhibited dose‐dependent knockdown with IC 50 s of 812.7 and 451.4 pM, which is comparable to wild‐type (IC 50 =439.7 pM) in the absence of red light, and IC 50 s of 562.9 and 354.5 pM, which is also comparable to wild‐type (IC 50 =337.4 pM), in the presence of red light. In addition, imaging studies with Ga‐(III)‐corrole‐modified siRNAs showed intense fluorescence in HeLa cells, highlighting that the Ga‐(III)‐corrole modification is an effective fluorophore for siRNA tracing and imaging. Moreover, the photodynamic activity of free base corrole vs the Ga‐(III)‐corrole was evaluated. Results show an increase of light cytotoxicity of the corrole ligand upon the addition of Ga‐(III); however, no phototoxicity was observed when Ga‐(III) ligands were linked to siRNA. In conclusion, Ga‐(III)‐corrole‐siRNAs show promising results for applications in simultaneous real‐time imaging and gene silencing.
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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".