Genome editing in kidney organoids

Genome editing has transformative potential for curing human diseases but poses unique challenges due to irreversible DNA alterations. Ensuring safe and effective in vivo editing requires preclinical studies to mitigate risks like genotoxicity, cytotoxicity, and immunogenicity. The kidney, highly susceptible to off-target effects due to its blood flow and exposure to systemic therapies, lacks established human models for assessing gene therapies. We utilized kidney organoids as a preclinical platform to test CRISPR/Cas9 genome editing via adeno-associated virus (AAV) delivery, a clinical strategy raising safety concerns due to toxic viral titers. We conduced RNA-seq to assess nephrotoxic responses. Overall design: RNA-seq profiling of untreated, AAV-GFP, and AAV-CRISPR/Cas9 kidney organoids.