If we know the exact mutation of the tumorous cells (do we?) is there a way to make that specific dna only malfunction? Seems risky because if it was not 100% specific all the time then could be lethal to normal cells. IE somehow add stop codons on the fusion protein part of the DNA so the fusion protein is never created. Delivery method though? Nucleus is hard to get to, protected fortress usually. [Nonsense-mediated decay - Wikipedia](https://en.wikipedia.org/wiki/Nonsense-mediated_decay) Like with this function of the ribosome where it eliminates aberrant mRNAs. Need to learn more. Cool - just read the wiki and it has the same idea here! ### Designing CRISPR-Cas9 experiments The implications of NMD are significant when designing CRISPR-Cas9 experiments, particularly those aimed at gene inactivation.[[17]](https://en.wikipedia.org/wiki/Nonsense-mediated_decay#cite_note-17) CRISPR-Cas9 introduces double-strand breaks that can lead to insertions or deletions (indels), often resulting in frameshift mutations and PTCs. If these PTCs are located in regions that trigger NMD, the resulting mRNAs will be rapidly degraded, leading to effective gene knockdown. However, if the PTCs are in regions that evade NMD, the mutant mRNAs may be translated into truncated proteins, potentially retaining partial function and leading to incomplete gene inactivation.[[14]](https://en.wikipedia.org/wiki/Nonsense-mediated_decay#cite_note-:0-14)[[18]](https://en.wikipedia.org/wiki/Nonsense-mediated_decay#cite_note-18) Therefore, understanding and incorporating NMD rules into the design of single guide RNAs (sgRNAs) is essential for achieving desired outcomes in CRISPR-Cas9 experiments. Tools such as NMDetective[[14]](https://en.wikipedia.org/wiki/Nonsense-mediated_decay#cite_note-:0-14) can predict the likelihood of NMD triggering based on the location of PTCs, thereby aiding in the design of more effective gene-editing strategies.