Genetic Kidney Diseases (GKDs) Modeling Using Genome Editing Technologies.

Area of Science:

• Genetics
• Molecular Biology
• Nephrology

Background:

• Genetic kidney diseases (GKDs) are rare, monogenic disorders affecting approximately 60-80 per 100,000 individuals.
• GKDs frequently cause early-onset chronic kidney disease, necessitating dialysis or transplantation.
• Current treatments for GKDs are limited, with no universal cure available.

Purpose of the Study:

• To describe the genetic causes and phenotypic effects of six representative GKDs.
• To review and compare site-specific nuclease systems for GKD modeling.
• To highlight advancements and obstacles in genome editing for GKD research.

Main Methods:

• Review of genetic causes and phenotypic effects of six GKDs (ciliopathy, glomerulopathy, tubulopathy).
• Comparison of genome editing tools: zinc finger nucleases (ZFNs), transcription activator-like effect nucleases (TALENs), and CRISPR-Cas9.
• Analysis of GKD model generation using these nucleases.

Main Results:

• Monogenic nature of most GKDs enables gene editing approaches.
• Genome editing systems have facilitated the creation of cellular and animal models of GKDs.
• These models have advanced understanding of GKD pathogenesis.

Conclusions:

• Genome editing technologies are crucial for developing GKD models.
• Understanding technological advances guides the selection of appropriate genome editing tools and delivery methods.
• Further research is needed to overcome obstacles for efficient GKD modeling and therapeutic development.