Many virus-based gene delivery systems have been developed to exploit viral transduction for inheritable or sustainable expression of a transgene in model organisms. The following table provides a comparison of key features of 4 major virus-based delivery systems, adenovirus, adeno-associated virus (AAV), retrovirus, and lentivirus. Each system has advantages and disadvantages. For examples, all 4 systems show broad tropism, capable of transducing a wdie range of host, tissue and cell types. Adenovirus has high transduction efficicency and is easy to amplify to high titers (>1012 TU/ml). Adenovirus does not integrate into the host genome, but it induces strong inflammatory response when administered in vivo. In contrast, AAV is almost non-pathogenic and triggers little or no immune response. However AAV has the smallest packaging capacity (4-5 kb only) among all 4 systems. Retrovirus can only transduce dividing cells, while other 3 systems can infect both dividing and non-dividing cells. A unique feature of retroviral and lentiviral systems is that they produce replication defective viral particles. This allows for the delivery of the desired transgene without continued viral replication in the target cells, thus, eliminating the dangers associated with the use of a live pathogen. However the risk of genome integration-induced mutagenesis and potential activation of oncogenesis limits the clincal applications of retroviral and lentiviral systems.
Comparison of Different Viral Gene Delivery Systems
Property | Adenovirus | AAV | Retrovirus | Lentivirus |
Viral genome | ssDNA | ssDNA | RNA | RNA |
Packaging capacity | ~8-30 kb | ~5 kb | ~7 kb | ~8 kb |
Transfection of non-dividing cells | yes | yes | no | yes |
Broad transducing tropism | yes | yes |
yes (dividing cells only) |
yes |
Inflammatory (immune) response | high | low/no | low | low |
Stable integration into host genome |
no (100% episomal) |
yes (>90% episomal) |
yes | yes |
Possibility to be pseudotyped | no | yes | yes | yes |
Duration of transgene expression in vivo |
Short (10 days to weeks) |
Long (2.5-6 months) |
Days to months |
Long (>12 months) |
Potential genotoxicity | Low | Low | Integration may induce oncogenesis | Integration may induce oncogenesis |
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