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This target refers to the genomic DNA and RNA of infectious agents, such as viruses, bacteria, and parasites, as well as residual donor white blood cells present in blood components intended for transfusion. In the field of transfusion medicine, these nucleic acids are the primary targets for pathogen reduction technologies (PRT) designed to enhance blood safety. By targeting the conserved structure of nucleic acids, these technologies aim to prevent the replication of pathogens and the proliferation of donor T-cells, which reduces the risk of transfusion-transmitted infections and transfusion-associated graft-versus-host disease (TA-GVHD) (Source: AABB Technical Manual; PubMed PMID: 25303825). Drugs or agents used in this process, such as amotosalen or riboflavin, typically intercalate into the DNA/RNA and, upon activation by ultraviolet light, form covalent cross-links or cause oxidative damage. This irreversible modification renders the genetic material non-functional, effectively inactivating the contaminant without significantly compromising the therapeutic function of the blood product, such as platelets or plasma, which lack functional nuclear DNA (Source: FDA, 2014; Cerus Corp). Consequently, this target is central to the manufacturing of pathogen-reduced blood products used globally to mitigate risks associated with known and emerging infectious threats.
The primary mechanism involves the intercalation of a photosensitizing agent into the double-stranded or single-stranded regions of DNA and RNA, followed by activation with ultraviolet (UV) light to form covalent cross-links or induce oxidative damage, thereby preventing replication and transcription (Source: FDA, 2014; Terumo BCT, 2021).
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