Hi Scott,
I have no position in ARIA, and hope that it does well, as I'm a gene therapy fan...but let me play Devil's advocate...
the inducible promoter in the RAPID construct produces the same level of therapeutic protein when 50% induced
Which promoter are you comparing it to? Is it a viral promoter (eg. CMV, SV40, etc)? An endogneous promoter? Does the promoter also contain all of the promoter enhancement regions? What if the transgene needs to be constitutively expressed? What if the timing or the length of expression is unknown?
Or why not use a spliceosome instead of replacing the whole gene, thus you would need a constitutive promoter to drive the transgene...and would not need RAPID as the cells endogenous promoter would be used?
RAPID's main usefulness would be if there was a mutation in the endogenous promoter/enhancer sequence causing irregular expression of the gene product. Why use RAPID instead of the endogenous promoter with the proper enhancement sequences? Shouldn't the endogenous promoter be preferred as mother nature selected for it?
AAV, lentiviral, or other vectors are shown to be CONSISTENTLY non-immunogenic, this rationale for using RAPID would be reduced.
The viral vectors are improving with each new generation, & if immunogenicity is a problem, then they are becoming less immunogenic(although there is potential for a neutralizing Ab response, even in AAV), just look @ the Helper Dependent Ad vector...there has been a study where they were able to give repeat administrations of the helper dependent ad vector and avoid the neutralizing Ab response, and also achieve long term expression(remember that this is a nonintegrating vector).
Why use RAPID over VLTS's inducible promoter? Or the Tet on or the Tet off inducible systems?
Best of Luck,
Where'd He Go?
BTW...What is subject of your dissertation? |
