Dit heb ik me het navolgende ook wel eens afgevraagd (en ook de antwoorden zijn interessant):
Vraag:
BOR (op het Yahoo forum):
"I'm not a biologist, but what's there to prevent TRiM platform from delivering mRNA or CRISPR payloads?"
Antwoorden:
Marc:
That is a good question from my perspective because I think that TRIM is what distinguishes ARWR from its competition and I would include NTLA and CRSP (as well as DRNA and ALNY) in that list. CAS-9 (and the other CAS) proteins used in CRSPR editing are much larger (higher molecular weight) and have much different chemistries (they might not form stable complexes with the TRIM ligands) than the short, double stranded RNA sequences used in interfering RNA's Although the chemical structure of TRIM is proprietary (thankfully, or else we would have more competition from the likes of DRNA and ALNY than we do now), I assume that the cartoon used to depict it on the ARWR website conveys the general idea, which consists of various ligands that modify the RNA trigger to make it more stable and more compatible with the target tissue. Thus, TRIM is actually many different molecular assemblies that differ in composition depending on the target. With respect to CRSPR, the CAS protein and guide strand have to get inside the nucleus where the DNA resides, whereas in the case of SiRNA, the trigger simply has to get into the cytoplasm (i.e., CAS-RNA guide strand complex has to penetrate two, very different types of membranes, rather than just one). With respect to mRNA therapeutics, mRNA is less stable than SiRNA, which would require additional modification of the TRIM platform. Nevertheless, I have stated in numerous previous posts that I think ARWR should consider developing mRNA therapeutics that complement their SiRNA's where this is possible, For example, in theory (it may not be possible), this would enable a therapeutic to simultaneously treat both alpha-1 antitrypsin deficiency liver and lung disease by blocking the formation of Z-AAT and promoting the formation of AAT via mRNA.
Hokiefun:
@Marc Interesting comments. Yeah I am so wondering what does the next platform or modifications look like in their pharmaceutical strategy. These are things we have not even seen yet put into clinical combinations but you can imagine where this technology is headed if the basics are handled well in regards to their singular strategy. I would dare say market cap of 500 to trillion is very real. Say you have 25 to 50 billion in annual sales then you have these combination actions flowing through the pipelines and they start adding to prevention, massive reductions in taking meds and the outcomes are much cleaner and more healthy for the patient in the long term. I am thinking exosomes will be key carrier and rnai in its forms will probably be the main component it just appears to be a much safer, cleaner, clearer outcome right now.