ArticleProceedings of the National Academy of Sciences of the United States of America2026
Charge-reversal proteolysis polymers enable tissue-specific STING degradation in rheumatoid arthritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Physicochemically-guided immunomodulatory biomaterials for regulating immune responses in rheumatoid arthritis.Materials today. Bio · 2026Article
- Signaling Pathway-Biomarker Coupling for Precision Therapy in Rheumatoid Arthritis: Mechanistic Insights, Translational Bottlenecks, and Emerging Strategies.ACR open rheumatology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Inhibiting stimulator of interferon genes (STING) is critical for treating rheumatoid arthritis (RA), yet achieving precise suppression with high tissue specificity across protein variants remains challenging. Here, we engineer a multilevel, intelligent STING degrader-charge-reversal proteolysis-targeting chimeras (CreTACs)-that efficiently delivers to RA sites and degrades STING variants in humans, mice, and rats. Unlike traditional degraders with systemic toxicity, this charge reversal platform leverages pH-programmed charge inversion: Electroneutrality in circulation (pH 7.4) minimizes toxicity, while acidic-triggered protonation enables a 7.5-fold increase in arthritic joint accumulation (tissue level), pH-gated cellular internalization (80% uptake at pH 6.5 vs. 50% at pH 7.4; cellular level), and enhanced cytoplasmic STING (proton channel) affinity via charge interactions (protein level). In collagen-induced arthritis models, CreTACs outperformed methotrexate by suppressing synovitis and bone erosion without hematological toxicity. This multilevel charge reversal strategy establishes a blueprint for next-generation proteolysis drug-delivery systems or biomaterials, offering transformative potential for healthcare.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.