ArticleMolecular therapy. Nucleic acids2025
Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Metal coordination at biological interfaces: Mechanisms, therapeutics, and translation.Materials today. Bio · 2026Review
- A New Avenue for the Long-Term Upstream Inhibition of the Renin-Angiotensin-Aldosterone System by Inhibiting Angiotensinogen RNA.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026Review
- Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing.Molecular therapy. Nucleic acids · 2026Article
- Design and systematic evaluation of novel chemical modification patterns enable the identification of a potent siRNA targetingMolecular therapy. Methods & clinical development · 2025Article
- An RNA interference therapeutic potentially achieves functional cure of chronic hepatitis B virus infection.Nature communications · 2025Article
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Authors and funding
7 authors.
Funding
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Abstract
Angiotensinogen (AGT) is the precursor of angiotensin II, a potent vasopressor in the renin-angiotensin-aldosterone system. Small interfering RNAs (siRNAs) targeting hepatic AGT can lower blood pressure in hypertension patients by reducing AGT levels, with effects lasting over 6 months. Existing siRNA molecules are effective, but novel ones with better inhibitory activity and longer duration periods may be developed. In this study, we demonstrated an entire development process for a novel siRNA targeting hepatic AGT. Through the proper combination of bioinformatic on-target/off-target screening on sequences, chemical modification patterns optimization, and liver-targeting delivery ligands conjugation, we have successfully developed several promising siRNAs with equivalent or better inhibitory activity, duration of effect, and safety profile compared with previously reported siRNA. Moreover, our comprehensive analysis has elucidated the correlation between the efficacy and free energy of siRNAs. Currently, there exists no reliable model capable of precisely predicting the activity and off-target risk associated with fully modified siRNAs. Therefore, the implementation of efficient screening procedures is of utmost importance during the development of siRNA candidates. This study presents a meticulous and valuable reference for the development of potent and safe siRNAs on other targets.
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