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Pathogen and donor leukocyte nucleic acids

Molecular classification
Nucleic acid, DNA, RNA
01

Overview

Pathogen and donor leukocyte nucleic acids are the primary molecular targets for pathogen reduction technologies (PRT) designed to enhance the safety of blood transfusions. These targets encompass the genomic DNA and RNA of various infectious agents—including viruses, bacteria, and parasites—as well as the DNA of residual donor white blood cells (Schlenke, 2014). By targeting these nucleic acids, PRTs aim to prevent the replication of pathogens and the proliferation of donor T-cells, thereby reducing the risk of transfusion-transmitted infections and transfusion-associated graft-versus-host disease (TA-GvHD) (Marschner & Goodrich, 2011). Therapeutic interventions typically involve the use of photoactive compounds like amotosalen or riboflavin, which intercalate into or bind to the nucleic acids and, upon activation by ultraviolet light, induce irreversible damage such as covalent cross-linking or oxidative lesions (Cerus Corporation; Terumo BCT). This approach provides a broad-spectrum safety measure that complements traditional screening methods by addressing both known and emerging threats in the blood supply. Furthermore, the inactivation of donor leukocyte nucleic acids serves as an effective alternative to gamma irradiation for preventing TA-GvHD in susceptible patients (PubMed, 2014).

Other names
Pathogen DNA and RNADonor leukocyte DNATransfusion-associated nucleic acidsNucleic acids of infectious agentsGenomic material of pathogens and leukocytes
02

Mechanism of action

Photoactivation-induced covalent cross-linking or oxidative modification of DNA and RNA, which inhibits strand separation and replication (Schlenke, 2014).

03

Biological functions

Genetic replicationTranscriptionTranslationImmune activationCellular proliferation
04

Disease associations

InfectionTransfusion-associated graft-versus-host diseaseSepsisViral hepatitisHIV/AIDSOther
05

Safety considerations

Potential toxicity of residual photoactive agents or photoproductsReduction in the therapeutic quality or recovery of blood components (e.g., platelets)Incomplete inactivation of certain non-enveloped virusesNeonatal sensitivity to photoactive metabolites
06

Interacting drugs

Amotosalen

2 more in the full profile.

07

Biomarkers

Residual leukocyte countPathogen load (viral/bacterial DNA/RNA levels)Nucleic acid adduct formationLog reduction of infectious titers

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