Despite extensive donor screening and improved tests for blood transfusion-associated diseases such as hepatitis and HIV remain significant problems. As a result, the development of an efficient and safe process for the decontamination of blood comDonents has become a goal o several research efforts. We have developed experimental protocols for a psoralen-based photochemical decontamination process for platelet concentrates utilizing UVA light. The best candidate identified for viral inactivation was, however, also unacceptably mutagenic, as defined by the Ames assay. We have now discovered several compounds with significant anti-HIV activity under photodecontamination conditions that show less mutagenicity. We seek to identify further compounds with enhanced activity and even lower mutagenicity for commercialization in the decontamination of platelet suspensions. This objective will be achieved through the following specific aims: I) synthesis of at least 20 new psoralens with potential for improvement by both above criteria; 2) evaTuation of the photoinactivating potential of the compounds with a bacteriophage model. Successful compounds will be further tested in a photoinactivation assay against HIV-I, as well; 3) evaluation of each compound in an Ames assay with both bacteria sensitive to frame shift mutagens and those sensitive to base substitution mutagens.Awardee's statement of the potential commercial applications of the research:Our long-term objective is to develop universally applicable photochemical methods for the decontamination of human blood products. Presently, over 13 million units of blood are collected annually, providing approximately 7 million units of platelets for transfusion. While the current protection of the blood sul ply depends on testing, a decontamination strategy could limit the introduction of new tests and ensure the future safety of the blood supply against new pathogens. An efficient and practical method to decontaminate platelets would clearly provide a significant commercial opportunity.National Heart, Lung, and Blood Institute (NHLBI)
