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

Project Information

xenCAKUT

Grant agreement ID: 891127

DOI

10.3030/891127

Project closed

EC signature date 6 March 2020

Start date 1 October 2020

End date 30 September 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 191 149,44

EU contribution

€ 191 149,44

Coordinated by

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)

Reporting period: 2020-10-01 to 2022-09-30

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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)

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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