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1st, 2nd Generations vs. Gutless Adenovirus Systems

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Map of adenovirus serotype 5 genome and different generations of adenoviral vectors. Early transcripts are represented by E1–E4 regions and late transcripts are represented by L1–L5 regions. MLP: major late promoter; Psi: packaging signal.

First-generation system:
– Two adenoviral early genes, E1 and E3, are deleted
– Transgene expression istransient and the vector is quickly lost in cells
– Causes high cytotoxicity or immune response

– A single step of homologous recombination between the vector and host genome sequence may give rise to RCA generation

Second-generation system:
– Additional essential genes, E2 and E4 are deleted in addition to E1 and E3
– Transgene is expressed at a higher lever for a longer duration
– Diminished cytotoxicity or immune response
– Deletion of E4 and E2 genes which are essential for adenoviral growth and replication further reduces the potential RCA generation

 

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