Preclinical and clinical developments in enzyme-loaded red blood cells: an update

Abstract

Introduction: We have previously described the preclinical developments in enzyme-loaded red blood cells to be used in the treatment of several rare diseases, as well as in chronic conditions.

Area covered: Since our previous publication we have seen further progress in the previously discussed approaches and, interestingly enough, in additional new studies that further strengthen the idea that red blood cell-based therapeutics may have unique advantages over conventional enzyme replacement therapies in terms of efficacy and safety. Here we highlight these investigations and compare, when possible, the reported results versus the current therapeutic approaches.

Expert opinion: The continuous increase in the number of new potential applications and the progress from the encapsulation of a single enzyme to the engineering of an entire metabolic pathway open the field to unexpected developments and confirm the role of red blood cells as cellular bioreactors that can be conveniently manipulated to acquire useful therapeutic metabolic abilities. Positioning of these new approaches versus newly approved drugs is essential for the successful transition of this technology from the preclinical to the clinical stage and hopefully to final approval.

Keywords: Drug-loaded RBCs; RBC-derived extracellular vesicles; cancer therapy; enzyme replacement therapy; guanidinoacetate methyltransferase deficiency; metabolic diseases; therapeutic protein delivery; toxic molecule removal.