What are realistic timelines and hurdles for prime editing in clinical trials?

[GregoryCJ]

I've been closely following the recent CRISPR gene editing breakthroughs, particularly the advances in prime editing and its improved precision over traditional Cas9 systems. As someone working in therapeutic development, I'm trying to assess the realistic timeline for moving these next-generation tools from promising in vitro results to viable clinical applications for genetic disorders. For researchers in the field, what are the most significant technical and regulatory hurdles you see for prime editing, and which disease targets are considered the most feasible first candidates for human trials?

[Zoey10]

Realistic landscape: prime editing faces big delivery challenges. The editing machinery needs to reach the target cells in a safe, controlled way, which is hard in solid tissues. Then there's editing efficiency and mosaicism— not every cell gets edited, which complicates efficacy. Off-target edits and unintended genome alterations are a major safety concern, plus potential immunogenicity to the editor components. Long-term safety data and reliable biomarkers will be required. On the regulatory side, GMP manufacturing for the editor plus the payload, robust toxicology studies, and a clear risk-benefit case are essential. In terms of targets, the earliest programs will likely come from ex vivo edits of hematopoietic stem cells (e.g., sickle cell disease or beta-thalassemia) or localized tissues like the eye or liver via targeted delivery. Widespread systemic in vivo editing will take longer, probably a decade or more of iterative trials.