NixOS has containers that show how this could work, but they're only via systemd-nspawn, so not as jailed as Qube's domUs.
I've also been looking at how projects like Hypercontainer and Clear Containers achieve minimal VM overhead to expand the model to a per-application-instance VM.
Another interesting enabling technology is VirtFS, which can be used for filesystem-level storage virtualization to gain the many benefits of COW and shared caching.
The principal question then is how to allow interaction between different application instances without the user having to manually ferry files between them, as it currently happens with AppVMs on Qubes.