Investigation of E. coli-mediated intracellular GLA gene delivery and extracellular rhα-Gal A enzyme production strategies for Fabry disease

Fabry disease is a x-linked genetic disorder caused due to the mutation in GLA gene, which disrupts the production of an enzyme called α-Gal A, leading to the accumulation of toxic materials (Gb3) in cells and the deterioration of organs. Currently available treatments are useful but costly. This project investigated a scalable, genetically modified strain of E. coli to deliver the deficient gene within Fabry cells to complement the Fabry defect. Gene delivery by cell wall-deficient invasive E. coli restored enzyme function in Fabry cells, reduced Gb3 accumulation, and reduced cellular oxidative stress to the non-Fabry level. However, when trying to extracellularly produce rhα-Gal A enzyme in the same strain, no enzymatic activity was observed. Therefore, Further optimizations are required to successfully produce an active enzyme. This system potentially provides a tunable, cost-effective alternative for Fabry and similar diseases.