Cytosolic Delivery of Argininosuccinate Synthetase Using a Cell-Permeant Miniature Protein
Susan L. Knox, Rebecca F. Wissner, Samantha Piszkiewicz, Alanna Schepartz
Abstract
, stabilized in plasma, and traffics successfully to the cytosol of cultured Saos-2 and SK-HEP-1 cells, achieving cytosolic concentrations greater than 100 nM. This value is 3-10-fold higher than the concentration of endogenous AS (11 ± 1 to 44 ± 5 nM). When injected into healthy C57BL/6 mice, ZF-AS reaches the mouse liver to establish concentrations almost 200 nM above baseline. These studies demonstrate that ZF5.3 can deliver a complex enzyme to the cytosol at therapeutically relevant concentrations and support its application as an improved delivery vehicle for therapeutic proteins that function in the cytosol, including enzyme replacement therapies.
Topics & Concepts
CytosolArgininosuccinate synthaseCitrullinemiaArgininosuccinate lyaseUrea cycleChemistryEnzymeBiochemistryFusion proteinArginineIn vitroArginaseLactate dehydrogenaseAmino acidRecombinant DNAGeneVirus-based gene therapy researchRNA Interference and Gene DeliveryCancer Research and Treatments