Bacterial contamination and emerging infections combined with increased international travel pose a great risk to the safety of the blood supply. Tests to detect the presence of infection in a donor have a ‘window period’ during which infections cannot be detected but the donor may be infectious. Agents and their transmission routes need to be recognized before specific tests can be developed. Pathogen reduction of blood components represents a means to address these concerns and is a proactive approach for the prevention of transfusion-transmitted diseases. The expectation of a pathogen reduction system is that it achieves high enough levels of pathogen reduction to reduce or prevent the likelihood of disease transmission while preserving adequate cell and protein quality. In addition the system needs to be nontoxic, non-mutagenic and should be simple to use. The Mirasol® Pathogen Reduction Technology (PRT) System for Platelets and Plasma uses riboflavin (vitamin B2) plus UV light to induce damage in nucleic acid-containing agents. The system has been shown to be effective against clinically relevant pathogens and inactivates leukocytes without significantly compromising the efficacy of the product or resulting in product loss. Riboflavin is a naturally occurring vitamin with a well-known and well-characterized safety profile. The same methodology is currently under development for the treatment of whole blood, making pathogen reduction of all blood products using one system achievable. This review gives an overview of the Mirasol PRT System, summarizing the mechanism of action, toxicology profile, pathogen reduction performance and clinical efficacy of the process.

We are developing a technology based on the combined application of riboflavin (RB) and light for inactivating pathogens in blood products while retaining the biological functions of the treated cells and proteins. Virus and bacteria reduction measured by tissue culture infectivity or colony formation with UV light alone and in combination with RB yield equivalent results. The effects of RB as a sensitizing agent on DNA in white cells, bacteria and viruses in combination with UV light exposure have been evaluated. UV-mediated DNA degradation in Jurkat T cells and leukocytes in plasma as measured by the FlowTACS assay was significantly increased in the presence of RB. Agarose gel electrophoretic analysis of DNA in Escherichia coli and leukocytes in plasma demonstrated enhanced DNA degradation in the presence of RB. UV light in combination with RB prevented the reactivation of lambda phage compared with samples irradiated in the absence of RB. UV-mediated oxidative damage in calf thymus DNA was also enhanced in the presence of RB. These observations clearly demonstrate that the presence of RB and UV light selectively enhances damage to the guanine bases in DNA. These data also suggest that the type and extent of damage to DNA for virus in the presence of RB and light make it less likely to be repaired by normal repair pathways available in host cells.