> So how does Cas12a2 mitigate off-target effects?

Others in this thread may be able to give a better analogy, but I'll try:

Cas9 is like open heart surgery on millions of cells all at once. We know the specific outcome we want - a surgical replacement of a sliver of a sequence - but just like open heart surgery, it's an inexact operation. Cas9 tolerates mismatches which categorically allows off-target matching. It also operates on DNA, so any off-target effects reprogram the cell's primary source code.

We want the Cas9 "patient" cell to survive.

In contrast, Cas12a2 is key-locked self-destruction switch. It targets single-stranded RNA transcripts with a specific guide protein. So the specificity is two-fold: the guide protein doesn't tolerate mismatches, and its operating on a _downstream byproduct_ of the DNA. When the key (guide protein) matches, it unleashes total destruction within the cell.

We want the Cas12a2 "patient" cell to die.

> If it were to work, gene therapy would be an accurate - and affordable - technique. Which it is not right now.

Correct on the first point. If it were to work, gene therapy could be more common. I do not know how to make it affordable, yet. In the models I've built to commercialize this I estimate a Cas12a2 treatment would cost approximately as much as a bone marrow transplant.

> How does "answering questions" offset the technology being inferior right now?

In fairness, asking and seeking answers to questions is all I have right now. There is no cure to my disease so the upside - no matter how futile you may perceive it to be - to me, is infinite.

If I can solve it I may get a few more years with my daughter. If I can't, I can show her how to live fighting for an answer that may never come.

You're not wrong, you and I just have different perspectives on the upside.