Table 3.

How cell type may determine the risk of insertional mutagenesis

LevelBefore insertionAfter insertion
Genome Number of pre-existing mutations Potential for secondary mutations 
 Number and size of activated, potentially disruptible “dangerous” loci susceptible to transgene insertion Proliferation capacity/propensity  
Cell-transgene interactions, direct Host factors participating in preintegration complex Recognition of transgene regulatory elements and expression level of transgene  
 Cell-cycle status Type and number of mechanisms supporting transgene side effect  
Cellular response, indirect  Response balance to “danger” signals 
  Potential for escape from senescence  
  Number of generations following genetic modification  
  Level of differentiation 
LevelBefore insertionAfter insertion
Genome Number of pre-existing mutations Potential for secondary mutations 
 Number and size of activated, potentially disruptible “dangerous” loci susceptible to transgene insertion Proliferation capacity/propensity  
Cell-transgene interactions, direct Host factors participating in preintegration complex Recognition of transgene regulatory elements and expression level of transgene  
 Cell-cycle status Type and number of mechanisms supporting transgene side effect  
Cellular response, indirect  Response balance to “danger” signals 
  Potential for escape from senescence  
  Number of generations following genetic modification  
  Level of differentiation 

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