Ask HN: Would it be possible to use QubesOS with Silverblue and Nix/Guix?

Fedora Silverblue provides an immutable base system, which makes it easier and faster to upgrade. That in itself looks like a great feature to use as a TemplateVM on QubesOS.

The problem is that since the base image is immutable, the way you install apps is via rpm-ostree layers, which you sould use sparingly, or FlatPak/AppImage or containers (podman/docker/toolbox).

FlatPak has its own problems (https://flatkill.org/, https://flatkill.org/2020/)

Nix/Guix seems like a more elegant way to overlaying new apps on the system in a more controlled/secure way.

Would it be possible to combine these technologies, QubesOS with a Fedora Silverblue TemplateVM (maybe even for Dom0) and use Nix or Guix to install packages? Would it actually make sense to do so? What would be the potential issues or drawbacks of doing that?