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Adeno Associated Virus (AAV) a) Advantages of AAV-mediated gene transfer
AAV has been developed into a very attractive candidate for creating viral vectors for gene therapy and the creation of isogenic human disease models due to various advantages. 1) Superior biosafety rating. The wild type AAV has not currently been known to cause disease in vivo, and further security of recombinant AAV gene delivery in vivo is ensured after removal of most AAV genome elements. 2) Low immunogenicity. AAV causes a very mild immune response in vivo, lending further support to its apparent lack of pathogenicity during gene delivery. 3) Broad range of infectivity. AAV can infect both dividing and quiescent cells in vivo, allowing gene delivery to a highly diverse range of cell types. 4) Stable expression. Long term gene delivery in vivo can be mediated by AAV. b) Drawbacks of AAV-mediated gene transfer
Although adenovirus benefits a great deal of disease therapies, it does present some drawbacks.
1) The major drawback is its limited cloning capacity (less than 4.7kb) of the vector, which restricts its use in gene delivery of large genes.(Table 3) [32]. 2) Generation of neutralizing antibodies against AAV in the Non-Human Primates (NHP) and human, may attenuate the cure effect of AAV-mediated gene therapy [33].

Table 2. Comparison between Retrovirus, Lentivirus, Adenovirus and Adeno-associated virus (AAV) vectors.
Comparison Retrovirus Lentivirus Adenovirus AAV
Genome ss RNA ss RNA ds DNA ss DNA
Integration Yes Yes No No
Packaging Capacity 3kb 4kb 5.5kb 2kb
Time to peak expression 72h 72h 36h-72h Cell: 7 days;
Animals: 2 weeks
Sustainable time About 3 weeks Stable expression Transient expression > 6 months
Cell Type Most Dividing Most Dividing/Non-Dividing Cells Most Dividing/Non-Dividing Cells Most Dividing/Non-Dividing Cells
Titer 10^7 TU/ml 10^8 TU/ml 10^11 PFU/ml 10^12 vg/ml
Animal experiment Suitable Low efficiency Lowest efficiency Most suitable
Immune Response High Medium Medium Ultra-low

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