Overall, I’ve heard it’s very hard to infect microglia with virus.
Peter Grace has done it
How are you delivering? Intraspinal? Intrathecal? What is AAV2/TM6? Is that some special serotype?
I feel like this is going to be very challenging.
This review looks good and recent and outlines the challenges and tools
From the paper:
In summary, less than 20% AAV transduction efficiency can be achieved in vivo (Table 2), confirming that AAV transduction of microglia is challenging. This observation aligns with other publications that have focused on improving in vivo AAV transduction for other CNS cell types. Most approaches report a lack of microglial transduction upon different delivery strategies, including intrastriatal injection , systemic delivery [58,59], or neonatal intracerebroventricular delivery [40,60]. Only a few studies describe minimal microglial transduction without further quantification [41,61]. Although AAVs seem to be the preferred option for targeting neurons, extensive research is still needed to improve in vivo transduction efficiency in microglia.
If I were you, I’d see if you can manipulate your GOI with transgenic methods and not viral. I know that’s probably not possible, but if it’s at all a consideration, try it. This seems like it’ll be a headache otherwise.
@tberta @esypek @thicunha Any thoughts?