Fundamentals of the psoralen-based Helinx technology for inactivation of infectious pathogens and leukocytes in platelets and plasma

Abstract

Psoralens plus ultraviolet A (UVA) light inactivate viruses and bacteria as well as leukocytes. A system employing the synthetic psoralen compound amotosalen hydrochloride (S-59), in combination with UVA light, is being developed to decontaminate platelet concentrates and plasma in a blood-bank setting. S-59 is a heterocyclic psoralen compound that reacts by a three-step process with nucleic acids (NAs): (1) S-59 intercalates into the double helix; (2) upon illumination with long-wavelength ultraviolet light (UVA), it covalently attaches to a single strand, forming a monoadduct; and (3) additional illumination causes a photoreaction of the monoadduct with the second NA strand, resulting in an interstrand crosslink. The reaction occurs with the genomic material of DNA- and RNA-based viruses and occurs in genomes that are single stranded as well as double stranded. Inactivation rate is related to genome size. Large genomes such as those in leukocytes are far more susceptible to inactivation than are viruses such as hepatitis B virus (HBV), which is inactivated (>10(5) logs) under conditions being developed for blood-bank use. The efficiency of the process is affected by a number of practical considerations such as solution components and light source. The S-59 photochemical treatment process (PCT) has been optimized for platelet concentrates as currently processed for transfusion.