NOAEL_MABEL t1_jcnk7vi wrote

You could look at its glycosylation. One of the things that makes you unique as a human are your patterns of glycans on your cell surface. For example, only humans and a few other extreme rare out outliers produce sialic acid while all other animals produce hydroxylated sialic acid. The glycome tells you a ton about what species you’re dealing with. You can tell the difference between bacteria vs fungi vs monkey vs fish vs human cells by looking at their sugars alone.


NOAEL_MABEL t1_jc8g7b9 wrote

This isn’t new, in fact, I believe the very first types of ‘cell therapies’ go as far back as the Egyptians when they noticed that tumors would shrink if you took pus and injected into a tumor. Of course the person died from sepsis, but it has been known for a long time that bacteria home towards the hypoxia environment in tumors and have anti-cancer properties. In fact, if you google hard enough you’ll find many companies out there who are pursuing this idea with genetically engineered live microbes for cancer treatments.


NOAEL_MABEL t1_jc38vig wrote

Yes, that’s why I wrote “in theory”. In reality, it isn’t that clean, even with modification.

Integration may not just be occurring at AAVS1, but all over the place. Studies have detected things like complex vector rearrangements and truncated vector genomes across multiple animals models inserted around transcriptional units. There seems to be no preference for gene coding regions and no clustering of integration sites.

In fact, The FDA had a CTGTAC meeting in 2021 to discuss these issues:


NOAEL_MABEL t1_jc2hhyb wrote

Crispr can do multiple things. If you want to shutoff a mutant gene, crispr cuts DNA that introduces mutations that eventually turn the gene off. Yes, you can also cut DNA and paste in a gene sequence with Crispr to fix faulty genes that you can’t just shutoff. There are also twists like Crispr base editors that can fix a single mutation without the need to cut DNA that causes a double strand break.

Contrast that to AAV. AAV doesn’t really integrate into a genome (well isn’t supposed to in theory) - they work by creating what’s known as an episome (i.e a circular piece of dna that persists in cells and gets translated into the desired protein). AAVs can only shutoff a mutant gene if they carry a payload like siRNA/microRNA or something. AAVs never really fix the mutant gene, the episome just expresses the protein that’s not working. I suppose over the long run AAVs might not really ‘cure’ a genetic disease, because the episome will likely dilute out over time with cell divisions. You can only really administer an AAV once too because of immunogenicity issues.

Also, you could use AAVs to deliver genes that encode for Crispr, so it isn’t like they’re mutually exclusive. There are pros and cons of using either of these approaches for a gene therapy. It depends on your strategy, target population, and overall risk.