Mincle-binding DNA aptamer demonstrates therapeutic potential in a model of inflammatory bowel disease
Notice bibliographique
Résumé
Pattern recognition receptors such as Mincle (Clec4e) play a significant role in the regulation of inflammation. Enhanced signaling of Mincle through the release of damage-associated molecular patterns during sterile inflammation has been shown to be important in the progression and manifestation of several diseases. A limitation to Mincle-targeted therapeutics is the feasibility of human-scale antibody therapy and the lack of alternative small-molecule inhibitors. Herein, we describe a highly specific neutralizing DNA aptamer targeting Mincle and demonstrate its therapeutic potential. Our data demonstrate that AptMincle selectively binds to both human and mouse Mincle with high affinity and is able to directly target and reduce Mincle activation. AptMincle can specifically reduce trehalose-6,6-dibehenate (TDB)-induced Syk and P65 phosphorylation in vitro in a manner comparable to that of the commercially available neutralizing antibody in vitro. Moreover, a bio-stable modified aptamer, AptMincleDRBL, was successful in reducing disease activity in a dextran sodium sulfate (DSS)-induced model of ulcerative colitis in a dose- and sequence-dependent manner. The results present an alternative, highly specific DNA aptamer with antagonistic function for use in the investigation of Mincle-associated diseases. The data also show the translational potential of Mincle-targeting aptamers as a new category of biologic therapy in the treatment of inflammatory bowel disease (IBD). Pattern recognition receptors such as Mincle (Clec4e) play a significant role in the regulation of inflammation. Enhanced signaling of Mincle through the release of damage-associated molecular patterns during sterile inflammation has been shown to be important in the progression and manifestation of several diseases. A limitation to Mincle-targeted therapeutics is the feasibility of human-scale antibody therapy and the lack of alternative small-molecule inhibitors. Herein, we describe a highly specific neutralizing DNA aptamer targeting Mincle and demonstrate its therapeutic potential. Our data demonstrate that AptMincle selectively binds to both human and mouse Mincle with high affinity and is able to directly target and reduce Mincle activation. AptMincle can specifically reduce trehalose-6,6-dibehenate (TDB)-induced Syk and P65 phosphorylation in vitro in a manner comparable to that of the commercially available neutralizing antibody in vitro. Moreover, a bio-stable modified aptamer, AptMincleDRBL, was successful in reducing disease activity in a dextran sodium sulfate (DSS)-induced model of ulcerative colitis in a dose- and sequence-dependent manner. The results present an alternative, highly specific DNA aptamer with antagonistic function for use in the investigation of Mincle-associated diseases. The data also show the translational potential of Mincle-targeting aptamers as a new category of biologic therapy in the treatment of inflammatory bowel disease (IBD).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».