Assemblers come with text substitution macros. Lisp comes with program rewriting macros. Same basic idea that it's all expanded away by runtime, but using something like scheme as the compile time metaprogram that emits the machine specific assembly. There are a few s-expression based assemblers out there so probably nothing novel.
Well Forth is possibly the most minimal VM over a platform, as evidenced by openfirmware.
It does have problems scaling though, in that if you've seen one Forth, you've seen one Forth ie. The variations required to fit a platform make them semi-incompatible.
Also, only global scope, no types and no built-in threadsafe constructs are limiting.
That's not to say that a more lispy Forth wouldn't be useful though, in that a concatenative syntax allows us to pass custom datastructures around like APL, and CPS (delimited continuations with lexically scoped dynamic binding would come from the lisp side (see https://github.com/manuel/wat-js).
