CRISPR/Cas9 based kidney disease modeling to elucidate novel genetic drivers and therapeutic targets in X. tropicalis

Informazioni relative al progetto

xenCAKUT

ID dell’accordo di sovvenzione: 891127

DOI

10.3030/891127

Progetto chiuso

Data della firma CE 6 Marzo 2020

Data di avvio 1 Ottobre 2020

Data di completamento 30 Settembre 2022

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 191 149,44

Contributo UE

€ 191 149,44

Coordinato da

UNIVERSITAT ZURICH
Switzerland

Periodic Reporting for period 1 - xenCAKUT (CRISPR/Cas9 based kidney disease modeling to elucidate novel genetic drivers and therapeutic targets in X. tropicalis)

Periodo di rendicontazione: 2020-10-01 al 2022-09-30

Sintesi del contesto e degli obiettivi generali del progetto

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) collectively refer to a diverse group of malformations occurring during embryonic kidney and urinary tract development which underlie a major percentage (40%) of paediatric end-stage renal disease (ESRD) cases. CAKUT is also significant contributing factor to chronic kidney disease (CKD) in adults. CKD is becoming an increasing challenge for the European healthcare systems as it is estimated that between 3.3% and 17.3% of the EU population has reduced kidney function and is at high risk of becoming dependent on renal replacement therapies. In xenCAKUT, we intended to yield insight in the genetics of kidney disease using the amphibian animal model xenopus tropicalis.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Using genome editing techniques we generated new animal models for autosomal polycystic kidney disease (ADPKD). Further, we established pipelines for automated analysis of cystogenesis in these models using deep learning artificial intelligence (AI) approaches. These novel models have yielded significant new insights into ADPKD pathogenesis and were used to assess the involvement of potential modifier genes. Results where disseminated by publications in specialized scientific journals (Such as Development)

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

ADPKD represents the most common monogenetic disease (incidence 1:500-1:1000) and is a frequent cause of end-stage renal disease (ESRD). The xenCAKUT project achieved significant progress beyond the state of the art, establishing novel animal models for ADPKD and the AI tools to analyze these further. Together, these can lead the way towards novel treatment strategies for ADPKD.

Tadpole microscopy image showing the kidney in a Xenopus tropicalis tadpole