>Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells?
Yes, if the LNP could be engineered to target an essential surface receptor, which is still a very tough problem. It would also not solve the issue of the payload successfully entering the cell but being subsequently degraded.
>I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
This is essentially how treatment for chronic lymphocytic leukemia happens (hence why it's called "chronic"). People with CLL can stay on BTK inhibitors for decades, often until they die of other natural causes.
Interesting, thanks for the info!
Another question: how does this approach compare to trying to repair the pathogenic variants in the cancer? I asked here about that approach recently and the response was mainly about delivery difficulties: https://news.ycombinator.com/item?id=48285386
Even with 100% delivery efficacy, editing efficacy is nowhere near 100%. CRISPR/Cas editors will reliably detect the target sequence but will not reliably edit it in order to repair the mutant allele, whereas CRISPR/Cas12a2 will activate and destroy chromatin ~100% of the time when it detects the target.
As is often the case, it's a lot easier to indiscriminately destroy than precisely (re)build.