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Respiratory Diseases

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Synthetic peptide

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Top 5 Drug Type	Count

Synthetic peptide	1

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MAPKAPK2(MAP kinase-activated protein kinase 2)	1

ObjectiveThe human saphenous vein (HSV) is the most effective conduit for infrainguinal peripheral bypass grafting. Optimal vein graft preparation is critical to vein graft patency. Graft marking using surgical skin markers is detrimental to endothelial and smooth muscle function of the graft. The objective of this study was to evaluate the effect of FD&C Brilliant Blue No. 1 (FCF) as an alternative for vein graft marking.MethodsSegments of HSV were collected after typical harvest and graft preparation. The tissues were cut into rings and either left unmarked or marked with FCF (2.6 mM). The functional viability of the rings was determined in a muscle bath.Results Marking with FCF did not impair contractility of the smooth muscle (Figure 1A). Contractility was restored in HSV segments that had no functional contractile responses after harvest and preparation (Figure 1B). To determine the mechanism of this protective effect of FCF, purinergic receptors were activated with BzATP with and without pre-incubation with FCF (50μM) or a purinergic receptor antagonist (oATP, control) and the rise in [Ca 2+ ] i was measured. FCF and oATP reduced the BZATP-evoked rise in [Ca 2+ ] i (Figure 1C), suggesting that the salutary effects of FCF were due to inhibition of a P2X or P2Y receptor. ConclusionsFCF is a non-toxic alternative to surgical skin markers that antagonizes purinergic receptors in HSV. FCF restored functional viability to injured vascular smooth muscle. FCF may protect HSV against injury-elicited ‘danger’ signals such as extracellular ATP that is released during injury-induced preparation.

Nature CommunicationsQ1 · CROSS-FIELD

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

Q1 · CROSS-FIELD

ArticleOA

Author: Mukalel, Alvin J ; Hankenson, Kurt D ; Oliver, Matthew ; Lander, Cynthia ; Colazo, Juan M ; Evans, Brian C ; Fletcher, R Brock ; Ghimire, Kedar ; Isenberg, Jeffrey S ; Cheung-Flynn, Joyce ; Brophy, Colleen M ; Dailing, Eric A ; Duvall, Craig L ; Kilchrist, Kameron V ; Tierney, John W ; Gersbach, Charles A

AbstractPeptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo.

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100 Translational Medicine associated with Moerae Matrix, Inc.

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Pipeline

Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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