Advantages and Drawbacks of Adenovirus Vector-mediated Gene Transfer

a) Advantages of Adenovirus-mediated gene delivery

Adenovirus has been developed into a preferred candidate for creating viral vectors for gene therapy due to various advantages.
1) Well tolerated, with post-infection viability of the host cells being almost 100%.
2) Great packaging capacity (up to 8kb).
3) Broad range of infectivity. Adenovirus can infect both dividing and quiescent cells, allowing gene delivery to a highly diverse range of cell types.
4) It can be produced at high titer (10^10 VP/mL, which can be concentrated up to 10^13 VP/mL).
5) High infection efficiency. Almost 100% gene delivery in most cell types, completely surpassing other viral vector tools and liposome transfection.
6) Without integration into the host chromosome. Adenovirus remains epichromosomal in cells and does not inactivate genes or activate oncogenes.

b) Drawbacks of Adenovirus-mediated gene transfer

Although adenovirus benefits a great deal of disease therapies, it does present some drawbacks.
1) Adenovirus-mediated gene delivery may not sustain for long time, just transient expression.
2) Generation of neutralizing antibodies against adenovirus in the Non-Human Primates (NHP) and human, may attenuate the cure effect of adenovirus-mediated gene therapy [13].
3) Adenovirus vector infection can activate a wide variety of immune responses both humoral and cellular, which may increase the risk factor to use adenovirus as vectors in that high dose will result in acute toxicity and autoimmunity [14].
To date, the best solution for these drawbacks is to turn to Adeno associated virus (AAV) vectors, which can mediate long-term and stable expression and induce mild immune response, safer than adenovirus vectors.

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 3h-72h cell: 7 days; animals: 2 weeks
Sustainable time about 3 weeks stable expression transient expression > 6 months
Cell Type most dividing/non-dividing Cells 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 mild