AAV-mediated PIGO gene therapy

AAV-mediated PIGO gene therapy is an experimental gene therapy approach designed to treat inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) caused by mutations in the PIGO gene. The therapy utilizes an adeno-associated virus (AAV) vector to deliver a functional copy of the PIGO cDNA to affected cells, aiming to restore the biosynthesis of GPI-anchored proteins (GPI-APs). Research has explored various strategies, including simple gene replacement and homology-independent targeted integration (HITI) using CRISPR-Cas9 to ensure stable chromosomal integration and avoid potential toxicity from overexpression. Preclinical studies in mouse models have demonstrated the potential to reverse neurological symptoms such as growth retardation, motor dysfunction, and epilepsy. Optimization of vector design, including the use of the endogenous PIGO promoter and intracerebroventricular administration, has been shown to produce therapeutic effects while mitigating risks such as liver tumor formation observed with stronger, non-specific promoters.

Other names

AAV-PIGOPIGO gene therapy