As a lefty, I have yet to run across a framelock that I couldn't operate easily with my left hand. Sure, it's a little less safe, but framelocks are fairly ambidextrous, so long as the framelock/frame are fairly symmetrical.
I agreed with this, in some rare instances, such as the techno I find it to be easier.
That said, if Spyderco released any frame lock models as a lefty specific I would buy two of each.
Some like the domino, Slysz Bowie, and techno are in my opinion acceptable to operate as a lefty. The spyder flick is only possible that way.
Others, such as the southard, are an unfortunate impossibility.
There is really only three lock styles that are totally lefty friendly. Of those three Spyderco produces two. None of which are on my preferred Spyderco models that I EDC.
Learning to operate frame and liner locks as a left hander I feel gives me an advantage in the ability to truly be ambidextrous in the ability to operate these knives with either hand. I have used this ability on numerous occasions when only one hand was available.
All this rambling aside, I would love a lefty Ti millie, southard, domino, Bowie, whatever they could churn out.