alt Hacker NewsThere are two major problems, delivery is one of them. Collateral damage of mass cell destruction leading to systemic inflammation is the other.
The approach I'm reviewing now uses lipid nanoparticles (LNPs) for delivery. It isn't great for targeting my bone marrow condition but its workable. The team hasn't optimized it at all, either. There are also viral delivery mechanisms that I haven't studied yet.
The collateral damage problem is the backpressure on the delivery problem. If you get really good at delivery, you can destroy A LOT of cells very quickly. The human body (usually) responds to these events by releasing a lot of pro-inflammatory cytokines. This can lead to cytokine storms or worse.
As you "get good" at killing the target cells, the net effect can turn bad. It will probably be a balancing act.
Replies
Naively, I would deal with this by deciding how many cells I want to kill each day and then figure out a dosing schedule that achieves that. Or maybe it's better to do one dose every few days. But yeah either way.
Lipid nanoparticles are quite old as-is. How do you target cells specifically?
> If you get really good at delivery, you can destroy A LOT of cells very quickly.
You can destroy cells quickly. Ok. So the question is: how do you detect specifically only cancer cells via lipid nanoparticles? That was already a problem years ago with Herceptin. The rationale that is always used is that "we need to do something" for certain aggressive cancers. It has never been a super-effective technique, despite all the promo of how monoclonal antibodies are so accurate.
> As you "get good" at killing the target cells, the net effect can turn bad. It will probably be a balancing act.
That's already the status quo in the whole cancer field. I don't think that more than sloppy accuracy is acceptable for any gene therapy - and the off-target cleaving of CRISPR has always been the number #1 problem here.