[SPLICE-BETA] RNA splicing therapeutics for beta cell dysfunction and diabetes
Ente: European Commission
Scadenza: 2028-02-29
Importo max: 150.000 EUR
Paese: EU
Descrizione
Diabetes is a progressive metabolic disorder driven by beta cell dysfunction and failure, ultimately leading to chronic hyperglycemia and severe clinical complications. Current anti-diabetic treatments, including insulin secretagogues and incretin mimetics, primarily aim to control blood glucose levels without addressing the underlying molecular defects that drive beta cell decline, which in some cases even accelerate their exhaustion. Alternative splicing has recently emerged as a fundamental regulator of beta cell identity, glucose sensing, and insulin secretion, offering a novel therapeutic entry point. Our ERC-funded research uncovered a conserved program of islet-enriched microexons (IsletMICs), 3-51 nt exons controlling key genes in stimulus-secretion coupling. We have shown that splice-switching antisense oligonucleotides (SSOs) targeting specific IsletMICs can potentiate glucose-stimulated insulin secretion in human beta cells. This ERC PoC will advance a first-in-class RNA therapeutic for diabetes and other beta-cell related diseases through three integrated work packages: (1) develop a high-throughput screening pipeline to systematically test the effects of hundreds of SSOs on beta cell function; (2) targeted delivery using SSO-peptide conjugation and validation in primary human islets and hepatocytes for efficacy and toxicity in vitro studies; and (3) preclinical testing in a diabetic mouse model for biodistribution, safety, and glycemic control under a clinically relevant setting of beta cell dysfunction. By project completion, we will deliver a high-throughput platform for target discovery with subsequent decisive preclinical evidence, an optimised lead for selective beta cell delivery, and a roadmap for advancing into regulatory studies and engagement with pharmaceutical partners.
Vai al bando originale
Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.