Homorepeats, specifically polyglutamine (polyQ) and polyalanine (polyA), are often implicated in protein-protein interactions (PPIs). So far, a method to predict the participation of homorepeats in protein interactions is lacking. We propose a machine learning approach to identify PPI-involved polyQ and polyA regions within the human proteome based on known interacting regions. Using the dataset of human homorepeats, we identified 157 polyQ and 745 polyA regions potentially involved in PPIs. Machine learning models, trained on amino acid context and homorepeat length, demonstrated high precision (0.90-0.98) but variable recall (0.42-0.85). Random forest outperformed other models (AUC polyQ = 0.686, AUC polyA = 0.732) using the positions surrounding the homorepeat -10 to +10. Integrating paralog information marginally improved predictions but was excluded for model simplicity. Further optimization revealed that for polyQ, using amino acid surrounding positions from -6 to +6 increased AUC to 0.715. For polyA, no improvement was found. Incorporating coiled coil overlap information enhanced polyA predictions (AUC = 0.745) but not polyQ. Finally, we applied these models to predict PPI involvement across all polyQ and polyA regions, identifying potential interactions. Case studies illustrated the method's predictive capacity, highlighting known interacting regions with high scores and elucidating potential false negatives.

14 Mar 2023·ACS Nano

Use of a Liver-Targeting Immune-Tolerogenic mRNA Lipid Nanoparticle Platform to Treat Peanut-Induced Anaphylaxis by Single- and Multiple-Epitope Nucleotide Sequence Delivery

Article

Author: Liao, Yu-Pei ; Wang, Xiang ; Xia, Tian ; Luo, Lijia ; Xu, Xiao ; Nel, Andre E.

While oral desensitization is capable of alleviating peanut allergen anaphylaxis, long-term immune tolerance is the sought-after goal. We developed a liver-targeting lipid nanoparticle (LNP) platform to deliver mRNA-encoded peanut allergen epitopes to liver sinusoidal endothelial cells (LSECs), which function as robust tolerogenic antigen-presenting cells that induce FoxP3⁺ regulatory T-cells (Tregs). The mRNA strand was constructed by including nucleotide sequences encoding for nonallergenic MHC-II binding T-cell epitopes, identified in the dominant peanut allergen, Ara h2. These epitopes were inserted in the mRNA strand downstream of an MHC-II targeting sequence, further endowed in vitro with 5' and 3' capping sequences, a PolyA tail, and uridine substitution. Codon-optimized mRNA was used for microfluidics synthesis of LNPs with an ionizable cationic lipid, also decorated with a lipid-anchored mannose ligand for LSEC targeting. Biodistribution to the liver was confirmed by in vivo imaging, while ELISpot assays demonstrated an increase in IL-10-producing Tregs in the spleen. Prophylactic administration of tandem-repeat or a combination of encapsulated Ara h2 epitopes induced robust tolerogenic effects in C3H/HeJ mice, sensitized to and subsequently challenged with crude peanut allergen extract. In addition to alleviating physical manifestations of anaphylaxis, there was suppression of Th2-mediated cytokine production, IgE synthesis, and mast cell release, accompanied by increased IL-10 and TGF-β production in the peritoneum. Similar efficacy was demonstrated during LNP administration postsensitization. While nondecorated particles had lesser but significant effects, PolyA/LNP-Man lacked protective effects. These results demonstrate an exciting application of mRNA/LNP for treatment of food allergen anaphylaxis, with the promise to be widely applicable to the allergy field.

01 Dec 2022·BMC Plant Biology

Polyphosphate application influences morpho-physiological root traits involved in P acquisition and durum wheat growth performance

Article

Author: Delaplace, Pierre ; Tika, Asma ; Khourchi, Said ; Oukarroum, Abdallah ; Bargaz, Adnane

AbstractBackgroundAmong phosphate (P) fertilizers, polyphosphates (PolyPs) have shown promising results in terms of crop yield and plant P nutrition. However, compared to conventional P inputs, very little is known on the impact of PolyPs fertilizers on below- and above-ground plant functional traits involved in P acquisition. This study aims to evaluate agro-physiological responses of durum wheat variety ´Karim´ under different PolyPs applications. Three PolyPs fertilizers (PolyA, PolyB, and PolyC) versus one orthophosphate (OrthoP) were applied at three doses; 30 (D30), 60 (D60), and 90 (D90) kg P/ha under controlled conditions.The PolyPs (especially PolyB and PolyC) application at D60 significantly increased morphophysiological root traits (e.g., RL: 42 and 130%; RSA:40 and 60%), shoot inorganic P (Pi) content (159 and 88%), and root P acquisition efficiency (471 and 296%) under PolyB and PolyC, respectively compared to unfertilized plants. Above-ground physiological parameters, mainly nutrient acquisition, chlorophyll content and chlorophyll fluorescence parameters were also improved under PolyB and PolyA application at D60. A significant and positive correlation between shoot Pi content and rhizosphere soil acid phosphatase activity was observed, which reveal the key role of these enzymes in PolyPs (A and B) use efficiency. Furthermore, increased P uptake/RL ratio along with shoot Pi indicates more efficient P allocation to shoots with less investment in root biomass production under PolyPs (especially A and B).ConclusionsUnder our experimental conditions, these findings report positive impacts of PolyPs on wheat growth performance, particularly on photosynthesis and nutrient acquisition at D60, along with modulation of root morpho-physiological traits likely responsible of P acquisition efficiency.

100 Deals associated with Polyadenylic polyuridylic acid

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	NDA/BLA	FR	Ipsen SA	-
Breast Cancer	NDA/BLA	-	AIM ImmunoTech, Inc.	-
Hepatitis B	NDA/BLA	KR	Ipsen SA	-
HIV Infections	NDA/BLA	FR	Ipsen SA	-
Stomach Cancer	NDA/BLA	KR	Ipsen SA	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2006	Not Applicable	Node-positive breast cancer Adjuvant	336	Polyadenylic-polyuridylic acid	(iogiphdsha) = vspqnygzmk wrbsmmirew (gawhpfxcar, 45% - 91%) View more	Positive	20 Jun 2006
				polyadenylic-polyuridylic acid (No treatment)	(iogiphdsha) = uydsjiwtim wrbsmmirew (gawhpfxcar, 8% - 47%) View more

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