Trying to wrap my head around the potential re-administration of AAV with chimeric AAV | SGMO Message Board Posts

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Msg  128486 of 130734  at  6/19/2019 3:30:18 PM  by

Kabonk

The following message was updated on 6/19/2019 3:41:11 PM.

 In response to msg 128484 by  gg100
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Re: Trying to wrap my head around the potential re-administration of AAV with chimeric AAV

   
It's possible he was saying AAV re-dosing is possible today.  QURE doesn't seem overly concerned about moderate levels of antibodies to their AAV5 vector (based on NHP studies):
 
 
Later T-cell response against transfected cells could possibly be controlled with immunosuppressive steroids like is done now for initial dosing.
 
Right now, researchers are being cautious to avoid treating those with existing immunity to specific AAV vectors, but we won't know the full story for real until re-dosing is tried in humans with the same AAV vector.
 
Interesting paper about AAV re-dosing, "the elephant in the room" of gene therapy, using SVP-rapamycin in animals, co-administered with initial AAV to prevent antibodies and T-cell responses, thus allowing re-dosing:
 
 
Here is one of the publications from Selecta Bio:
 
 
Interesting that this effect is mediated by TRegs:
 
Our results suggest that SVP[Rapa] induces

a population of regulatory cells that mitigate immune responses

specific to the AAV serotype co-administered at the time of SVP

[Rapa] treatment and are capable of transferring tolerance to

naive recipients.

and there are lots of other, similar articles with varying strategies:
 
 
 
 
 
 
 
 


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Msg # Subject Author Recs Date Posted
128495 Re: Trying to wrap my head around the potential re-administration of AAV with chimeric AAV spaddy 0 6/19/2019 9:49:48 PM


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