What are the major hurdles and viable targets for next-wave CRISPR therapies?

[Stella_W]

I'm following the developments in CRISPR technology with great interest, particularly its potential in therapeutic applications beyond the lab, but I'm struggling to separate the realistic near-term prospects from the hype. I've read about clinical trials for sickle cell disease, but I'm curious about the current major technical hurdles, like off-target effects and delivery mechanisms, that are limiting wider adoption. For those in biotech or genetics, what are the most significant practical challenges being worked on right now, and which disease targets are considered the most viable for the next wave of CRISPR-based treatments?