Purpose of the review: Significant numbers of patients worldwide are affected by various rare diseases, but the effective treatment options to these individuals are limited. Rare diseases remain underfunded compared to more common diseases, leading to significant delays in research progress and ultimately, to finding an effective cure. Here, we review the use of genome-editing tools to understand the pathogenesis of rare diseases and develop additional therapeutic approaches with a high degree of precision.
Recent findings: Several genome-editing approaches, including CRISPR/Cas9, TALEN and ZFN, have been used to generate animal models of rare diseases, understand the disease pathogenesis, correct pathogenic mutations in patient-derived somatic cells and iPSCs, and develop new therapies for rare diseases. The CRISPR/Cas9 system stands out as the most extensively used method for genome editing due to its relative simplicity and superior efficiency compared to TALEN and ZFN. CRISPR/Cas9 is emerging as a feasible gene-editing option to treat rare monogenic and other genetically defined human diseases.
Summary: Less than 5% of ~7000 known rare diseases have FDA-approved therapies, providing a compelling need for additional research and clinical trials to identify efficient treatment options for patients with rare diseases. Development of efficient genome-editing tools capable to correct or replace dysfunctional genes will lead to novel therapeutic approaches in these diseases.
Keywords: CRISPR/Cas9; Genome editing; gene therapy; rare diseases.