Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy

• DOI: 10.1038/s41467-022-30847-x
• Publication Date: 2022-06-03T10:03:01Z
• Authors: Ryoko Kuwayama; Keiichiro Suzuki; Jun Nakamura; Emi Aizawa; Yoshichika Yoshioka; Masahito Ikawa; Shin Nabatame; Ken-ichi Inoue; Yoshiari Shimmyo; Keiichi Ozono; Taroh Kinoshita; Yoshiko Murakami
• Keywords: 0301 basic medicine; Glycosylphosphatidylinositols; Science; Q; Genetic Therapy; Immunoglobulin D; Article; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Seizures; Animals

AbstractInherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. As the clinical manifestations of IGD are systemic and lifelong lasting, we treated the mice with adeno-associated virus for homology-independent knock-in as well as extra-chromosomal expression of Pigo cDNA. Significant amelioration of neuronal phenotypes and growth defect was achieved, opening a new avenue for curing IGDs.