Research Project

Project Title:	From benchtop to preclinical trials. CRISPR/Cas9 to correct COL4A5 mutations causing Alport Syndrome in in-vitro and in-vivo dog and mouse model
Project Type:	Translational research
Disease group(s):	Hereditary glomerulopathies
Project Summary:	In order to find a cure for ATS, the proposed project aims to act on the molecular cause of the disease and to stably revert COL4 ATS causative mutations through the combination of the innovative CRISPR/Cas9 technology with the easily deliverable AAV system. Building upon the availability of dog and mouse animal model with specific mutation in COL4A5 and supported by recent data showing the efficacy of an AAV based-gene therapy the project aim to: -establish specificity and efficiency of the (AAV)-CRISPR/Cas9 gene therapy to restore the wild-type genotype in ATS mouse and dog in-vitro; -perform an in-vivo pilot trial on an ATS dog models and on a large cohort of mouse models, in order to achieve statistical significance, in collaboration with Dr. Nabity (Texas A&M University) and IRET Foundation in Bologna in order to evaluate the efficacy and safety of a CRISPR/Cas9 gene therapy approach. Evaluation of the gene therapy efficacy will be based on the ability to recovery of renal function and delay in worsening of clinical symptoms.
Lead principal investigator(s):	Alessandra Renieri, Siena
Co-investigator(s):	Sergio Daga , Siena Anna Maria Pinto, Siena
Project Period:	06/2021 - 05/2024
Sponsors:	Industry