Table 1.

Categories of side effects in the genetic manipulation of hematopoietic stem cells

LevelCategoryExample
Culture Loss of homing potential  
Vector Fusiogenic properties of viral envelope proteins  
Genotoxicity Insertional mutagenesis 
Phenotoxicity Interference of transgene product with cellular signaling networks  
Selection toxicity Side effects of regimens used to selectively engraft or expand manipulated cells 
Immune response Elimination of modified transgenic cells by antibodies or cytotoxic T cells directed against transgene-encoded antigens  
Interactions of 1-6 Cooperation of 3, 4, and 5 
LevelCategoryExample
Culture Loss of homing potential  
Vector Fusiogenic properties of viral envelope proteins  
Genotoxicity Insertional mutagenesis 
Phenotoxicity Interference of transgene product with cellular signaling networks  
Selection toxicity Side effects of regimens used to selectively engraft or expand manipulated cells 
Immune response Elimination of modified transgenic cells by antibodies or cytotoxic T cells directed against transgene-encoded antigens  
Interactions of 1-6 Cooperation of 3, 4, and 5 

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