Viral delivery targeting microglia

Hi guys,

Hope everyone is well during these strange times. Wondering if anyone knows of someone, or themselves have had any success with viral delivery targeting microglia? Trying to use an AAV2/TM6 shRNA virus to silence something in microglia (in a cre dependent manner), but it’s proven to be rather challenging.

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Hey @ShanTan
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 [44], 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?

Peter should have good answers and suggestions: We are testing various AAVs intrathecally to target DRG cells, but we will also collect spinal cord tissues and if we hit some microglia with one of these viruses I will let you know.

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@ShanTan - See replies

Wow, @achamess thank you so much for going out of your way to help me with this! I really appreciate it. Disappointed that the virus isn’t working for me, but I guess it’s kind of comforting that I’m not alone? Haha. Thanks again.