Choosing the Right Viral Vector
|Tropism||Dividing and Non-Dividing Cells||Dividing and Non-Dividing Cells|
|Packaging Capacity||~8.5 kb||~4.5 kb|
|Gene Expression||Transient||Potentially Long Lasting|
|Target Cell’s Immune Response||High||Very Low|
|Onset of Expression||16-24 Hours||2-7 Days (in vitro)|
3-21 Days (in vivo)
Ad5 vs. Ad(RGD)
Most cells can be infected using the standard Ad5, but there are some exceptions. Adenovirus infection is initiated by recognition of the native Ad5 receptor, coxsackievirus-adenovirus receptor (CAR), on target cells by the carboxy-terminal portion (i.e. knob) of the fiber protein. Therefore, the infection efficiency of adenoviruses is very low for cells with few or no CAR receptors.
The Arg-Gly-Asp (RGD) motif was introduced in the surface-exposed loops of adenovirus fiber knobs. This enables the virus to bypass CAR and mediate cell entry via RGD binding integrins. RGD adenoviruses can be used for “retargeting” cells in which regular adenoviruses don’t work well. The infection effeciency of RGD modified adenoviruses can be tens or hundreds of times higher than standard Ad5 in some cells, including human or mouse macrophages, T cells, synoviocytes, islet grafts, adipocytes, MEF, etc.
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