The goal is to develop practical psoralen-based photochemical decontamination (PCD) methods for inactivation of infectious pathogens in blood products. A prototype method using ultraviolet light (UVA) and 8-methoxypsoralen (8-MOP) was developed for platelet concentrates (PC). Although psoralens are highly specific for nucleic acid inactivation, the prototype technique is of limited utility due to stringent requirements for oxygen (O2) control during PCD to prevent production of active O2 species leading to blood constituent damage. There are 3 potential solutions: 1) reduction of O2 levels during PCD; 2) use of psoralens with limited active O2 species generation, eliminating O2 control; and 3) use of low psoralen concentrations and brief UVA exposures limiting active O2 species production. Phase II will extend evaluation of 4'- aminomethyl-4,5'-dimethyl-8-methoxypsoralen (AMMP) psoralen with enhanced nucleic acid affinity and decreased active O2 species production. Development of a low concentration 8-MOP-based PCD system for bacterial decontamination of PC will be pursued.
Specific aims are: 1) extend pathogen inactivation and platelet function studies with AMMP; 2) synthesize additional psoralens with improved properties; 3) evaluate effects of AMMP and other psoralens on in vitro platelet function following PCD and after PC storage; 4) evaluate in vitro function of platelets using a murine transfusion model; and 5) extend pathogen inactivation studies with the 8-MOP bactericidal system.
| Lin, L; Londe, H; Janda, J M et al. (1994) Photochemical inactivation of pathogenic bacteria in human platelet concentrates. Blood 83:2698-706 |
