What are the challenges for CRISPR/Cas9 system?

One limitation is the delivery of the Cas9/gRNA complex into an adequate number of cells. This drawback arises from the necessity to deliver all components into cells at appropriate concentrations and at the correct stage of the cell cycle. 

Another limitation is that, while rare, CRISPR/Cas edits may not always be accurate, resulting in off-target effects. These unintended changes can have severe consequences, especially in clinical settings where accuracy is crucial. A third drawback is that even when cells take in CRISPR/Cas, not all of them exhibit genome editing activity. This means that not every targeted cell will undergo the desired genetic modifications. Another challenge is the risk of triggering autoimmune responses due to unintended modifications of endogenous genes involved in immune regulation. Lastly, ethical concerns arise when using this technology, as it involves germline editing and heritable genetic modifications. The long-term risk involves unintentional alterations to an organism's genetic makeup that persist and are passed onto future generations.