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Pathogen inactivation via amotosalen and ultraviolet A treatment

Molecular classification
Other (Process utilizing a chemical agent amotosalen, not a single molecular target or receptor)
01

Overview

Pathogen inactivation via amotosalen/UVA treatment is a process for improving blood transfusion safety. It utilizes amotosalen, a photoactive chemical, and UVA light to irreversibly crosslink the nucleic acids of pathogens and residual leukocytes in collected platelet and plasma products. This blocks DNA/RNA replication, thereby preventing transfusion-transmitted infections and complications such as transfusion-associated graft-versus-host disease. Commercially implemented via the INTERCEPT Blood System, it inactivates a broad spectrum of bacteria, viruses (enveloped and non-enveloped), protozoa, and leukocytes. The method increases patient safety but may cause impaired platelet function, increased storage lesions, and may be less effective against certain multidrug-resistant bacteria with high efflux pump activity or against certain resilient viruses and spores. It is not a molecular target but a process with nucleic acids as its functional targets

Other names
amotosalen/UVA pathogen reductionINTERCEPT pathogen reductionphotochemical pathogen inactivation
02

Mechanism of action

Amotosalen intercalates with DNA/RNA, and upon UVA illumination, covalently cross-links nucleic acids, thus blocking replication and inactivating pathogens such as bacteria, viruses, parasites, and leukocytes

03

Biological functions

Pathogen inactivationDNA/RNA crosslinkingPrevention of pathogen replicationInactivation of leukocytes to prevent Graft-versus-Host Disease (TA-GVHD)
04

Disease associations

Infection (transfusion-transmitted infections)Prevention of graft-versus-host disease
05

Safety considerations

Reduced platelet function and survival (impaired aggregometry, increased apoptosis, faster clearance)Storage lesions—protein alterations accumulating in plateletsPotential gaps in inactivation of multidrug-resistant bacteria due to efflux pumps that remove amotosalen from bacterial cells, leading to resistance at clinically used concentrationsResistance in certain non-enveloped viruses (e.g., HAV, HEV, parvovirus B19, poliovirus) and bacterial spores (e.g., Bacillus cereus)No pathogen inactivation process eliminates all pathogens
06

Interacting drugs

Amotosalen
07

Biomarkers

None specific for patient selection or efficacy; however, platelet function markers (e.g., CD62P, GpIb levels) are affected and studied in quality control of treated blood products

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