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Pre-clinical proof of principle for orally delivered Th17 antagonist miniproteins

ABSTRACT: Pre-clinical proof of principle for orally delivered Th17 antagonist miniproteins

PROVIDER: PRJNA1096346 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28559800_1.fastq.gz	Fastqsanger.gz
	SRR28559800_2.fastq.gz	Fastqsanger.gz
	SRR28559801_1.fastq.gz	Fastqsanger.gz
	SRR28559801_2.fastq.gz	Fastqsanger.gz
	SRR28559802_1.fastq.gz	Fastqsanger.gz

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Pre-clinical proof of principle for orally delivered Th17 antagonist miniproteins

Project description:Interleukin (IL)-23 and IL-17 are well-validated therapeutic targets in autoinflammatory diseases. Antibodies targeting IL-23 and IL-17 have shown clinical efficacy but are limited by high costs, safety risks, lack of sustained efficacy, and poor patient convenience as they require parenteral administration. Here, we present designed miniproteins inhibiting IL-23R and IL-17 with antibody-like, low picomolar affinities at a fraction of the molecular size. The minibinders potently block cell signaling in vitro and are extremely stable, enabling oral administration and low-cost manufacturing. The orally administered IL-23R minibinder shows efficacy better than a clinical anti-IL-23 antibody in mouse colitis and has a favorable pharmacokinetics (PK) and biodistribution profile in rats. This work demonstrates that orally administered de novo-designed minibinders can reach a therapeutic target past the gut epithelial barrier. With high potency, gut stability, and straightforward manufacturability, de novo-designed minibinders are a promising modality for oral biologics.

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Preclinical proof of principle for orally delivered Th17 antagonist miniproteins.

Project description: Not available

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Project description:The complete genome sequence of the P. vivax Sal-1 strain allowed the design of a first version array representing 1 oligo/2 kb of coding sequences (http://zblab.sbs.ntu.edu.sg/vivax/index.html). Here, proof-of-principle experiments using total RNA of parasites obtained from the Sal-1 strain, from P. falciparum and from parasites obtained directly from two human patients are presented. To determine the extent of cross-hybridization of P. falciparum with P. vivax, and to determine overlaps in expression profiles of the P. vivax Sal1 monkey-adapted strain vs wild isolates, single dual hybridization analyses were performed.

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Proof of principle for iPS2-10X-seq: cardioids experiment during 3D cardiac differentiation

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