I'm thinking that, in order to build evidence in vivo, you will first need to target specific cell types, before unleashing a version of DRACO that could potentially affect infected cells that you wouldn't want to lose, like infected neurons.
Can different protein transduction tags be used to target different cell types?
Thanks and best wishes.
Yes, there's evidence that different transduction tags can be used to target different tissues. There are more than 1000 known transduction tags these days; it's an area of active interest and study.
The method of drug administration also has an effect on which tissues are targeted. For example, intranasal seems to target mainly the lungs and respiratory system.
Infected neurons are an interesting case. The immune system will already be trying to destroy them. Whether it's better to let the infection and immune processes continue, or to help the immune system by killing the infected cells is something we don't know yet, and will want to study. I could imagine cases where the answer could go either way, depending in part, for example, on the number of infected cells.
It's not the case that killing infected neurons is undesirable. An ideal example is probably rabies. The viruses traverse the peripheral nervous system, and then into the central nervous system, and ultimately into the brain with 100% mortality rate (unless stopped in time by administration of the vaccine.) Killing any infected neurons is the only way to stop the infection, and it's what a vaccine activated immune system response will do (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790004).
Thank you for your response. Actually, evolution has evolved a separate immune system for the brain, composed mainly of tissue-resident macrophages, that handle the lion's share of anti-infective strategies. This is distinct from the blood-borne immune system. While the blood-borne immune system's main tactic against viruses is to either apoptose or ingest the infected cell, the brain's immune system takes a radically different approach.
The brain's immune system focuses on containing the spread of the infection and triggering intracellular processes in the infected neurons that would intracellularly contain or destroy the virus while leaving the neuron intact. If you think about it, this makes sense. If we were to lose every neuron that was ever infected with any virus, we would be far too susceptible to brain damage and we would be constantly losing stored memories and the developmentally-embedded control algorithms that maintain homeostasis in the body.
Of course, in the most severe brain infections, the brain's immune system will call for backup from the blood-borne immune system, resulting in encephalitis. But this is the exception to the rule.
There is an unfortunate misconception that viral brain infections are rare. They are not. Because the blood-brain-barrier keeps out most of the blood-borne immune system, the brain is regarded as an "immune-privileged" organ, which makes it an ideal hiding place for neurotropic viruses such as measles or enteroviruses. Indeed, both measles virus RNA and enterovirus RNA can be isolated from brains decades after a "recovered" infection.
Good point. As I said above, encephalitis such as that due to rabies is the exception to the rule. Let's not forget that rabies "survivors" can be left with life-long neurological deficits.
That's very interesting, I'll read more about that.
One thing I'd note is that not every viral infection is going to be hitting the brain.
Another is that VTose would not be continuously administered. It would only affect virally infected brain cells during the administration time.
However, this is certainly an area that will need further thought over time and perhaps modifications to the molecule so that it doesn't pass through the blood-brain barrier.