Just something that might be interesting to read for those interested in CRISPR, using gold as a delivery instead of AAVs for permanent fixes to diseases that require genomic/epigenomic alteration. In this study it was conducted for blood stem cells, so the fix would be effectively permanent.
As efficient couriers, they could reduce the need for engineered viruses and specialized research centers. And that could help make these emerging, high-tech treatments accessible and affordable, said senior scientist Dr. Jennifer Adair
“Gene therapy has a lot of potential across many diseases, but the process we have right now is just not feasible in every place in the world,” Adair said. “We want to end up delivering gene therapy in a syringe. This gold nanoparticle represents the first possibility we have to do that for blood stem cells.”
The effect can also rescue mice from the exaggerated repetitive behaviours caused by fragile X syndrome, a common single-gene form of autism spectrum disorders. CRISPR–Gold may significantly accelerate the development of brain-targeted therapeutics
Well, this is speculation, I am not a forum guru who has worked it all out and can give you the magic beans on this one, but my guess would be that something like the tet1 dcas9 fusion could form a basis of something useful for us eventually. There’s only one epigenetic modification that could be playing the critical role in this in my view and that’s methylation, as methylation can be effectively permanent (without altering the underlying code). Methyl groups are attached to DNA at the CpG island promotor regions of a gene and function repressively, with more meaning more repression of gene expression. Like grapes being put on a baseball. Maybe I’ll make some basic posts on steroid biology, epigenetics and neurotransmission when I’ve finished what I’m doing. I could not effectively understand site specific variability or interpret studies without spending pretty much a year on a basic education, so it might be useful to others. Anyway…Given we don’t know where these key loci are this is pretty blue sky thinking, but in principle something like this would possibly be applicable:
When the optimal design was reached, the system behaved as expected and only “tenuous off-target effects” were observed. The dCas9-TET1 system was shown to work in HEK-293FT, SH-SY5Y, and HeLa cell lines. The team also confirmed the functionality of their system by deactivating the TET1-CD. Ultimately, this designer system demonstrates the powerful potential that sgRNA 2.0 and aptamers offer up to any CRISPR-based system. dCas9-TET1’s ability to easily target genes of choice will enable new experimentation into the basic functional roles of DNA demethylation, such as screens of gene promoters. It could also enable the development of precision medicine.
More recently, an easier system had been developed with much less off target effects as there was not the implicit need to transfect the TET1 enzyme, which could have other effects. It worked by placing some short RNA’s that would inhibit DNMT1 at the specific loci:
The important takeaway from this I think is twofold: One, this technology is cheap and massively adopted. That’s its strength, and why it’s taken many bioindustries by storm. We’re going to start seeing the world change in the next few years because of it in a lot of areas, I’m quite sure. Secondly, it’s very adaptable and is inherently a programmable system. A lot of users say “a pill will never be developed!”, either in despair or trying to promote this or that idea. I think what a lot of the emergent biotech shown as effective in living animals highlights is that it doesn’t entirely matter if “a drug will never be developed”, and that the traditional track of drug development from scratch likely wouldn’t be applicable anyway. That’s not to say there might not be drugs effective for the condition. Rather, there may be ways and systems that can be easily and cheaply adapted in the future that might not immediately spring to everyone’s mind. That’s why it’s so important we get to grips with the actual issue at the molecular level, and get the right people looking at it in the meantime.
Also it’s pretty interesting science regardless.
Thanks for the reply. It’s encouraging to know that there is something that in theory can help us eventually, but like you said it’s premature to get too excited at this stage until we know exactly what/ where is affected in our bodies
