CRISPR
Explore the fascinating world of CRISPR technology
CRISPR: Short for “clustered regularly interspaced short palindromic repeats”, CRISPR is a groundbreaking technique used by scientists to edit the DNA of living organisms with precision. This technology holds great potential for therapeutic gene correction in Lesch-Nyhan Syndrome.
Exploring Therapeutic Gene Correction: Delve into the innovative use of CRISPR for gene correction in Lesch-Nyhan Syndrome, highlighting the potential of base and prime editing techniques.
Advancing with Human Embryonic Stem Cells: Discover how CRISPR/Cas9 is being utilized to create human embryonic stem cell sub-lines, advancing research in modeling Lesch-Nyhan disease.
National Human Genome Research Institute: This link underlines the ongoing commitment to genomic research, which is integral to understanding and tackling this complex genetic disorder.
Research Articles
March 14, 2023
Therapeutic gene correction for Lesch-Nyhan syndrome using CRISPR-mediated base and prime editing
Abstract
Lesch-Nyhan syndrome (LNS) is inherited as an X-linked recessive genetic disorder caused by mutations in hypoxanthine-guanine phosphoribosyl transferase 1 (HPRT1). Patients with LNS show various clinical phenotypes, including hyperuricemia, gout, devastating behavioral abnormality, intellectual disability, and self-harm. Although uric acid overproduction can be modulated with the xanthine oxidase inhibitor allopurinol, there exists no treatment for behavioral and neurological manifestations of LNS. In the current study, CRISPR-mediated base editors (BEs) and prime editors (PEs) were utilized to generate LNS-associated disease models and correct the disease models for therapeutic approach. Cytosine BEs (CBEs) were used to induce c.430C>T and c.508C>T mutations in HAP1 cells, and then adenine BEs (ABEs) were used to correct these mutations without DNA cleavage. PEs induced a c.333_334ins(A) mutation, identified in a Korean patient with LNS, in HAP1 cells, which was corrected in turn by PEs. Furthermore, improved PEs corrected the same mutation in LNS patient-derived fibroblasts by up to 14% without any unwanted mutations. These results suggest that CRISPR-mediated BEs and PEs would be suggested as a potential therapeutic strategy of this extremely rare, devastating genetic disease.