Strictly speaking, no, self-sponsorship is prohibited in the H-1B context. But if you have cofounders, own less than 50%, set up an independent board, etc., it could work.

By an independent board do you mean that the H1B holder cannot themselves be on the company's board? Re: 50% ownership, is 50-50 split OK, or does it have to be less than 50?

If the cofounders are family members(w US citizenship) would it raise red-flags for collusion?

Not so much collusion as concerns about whether they are really independent of the foreign national cofounder.

Independent in what way? Capital, expertise or not sharing any family ties at all?

Independent in the sense that their ownership/control isn't really just your ownership/control.