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All of Sergiy Velychko's Comments + Replies

Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible
Sergiy Velychko111
  • Do the rates of full-term and adult survival rates in iPSC mice match that which could be achieved by normal IVF, or do they indicate that there is still some suboptimality in culturing of tetraploid aggregated iPSC embryos? I'm not familiar with the normal rates of survival for mice so I wasn't able to tell from the graph whether there is still room for improvement.

Using tetraploid complementation, it is possible to achieve up to 70% of full-term development, which is similar rate of mouse natural conception. And this was before we understood how it works... (read more)

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Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible
Sergiy Velychko162

None of the stuff that you suggested has worked for any animal. I'm not saying it's impossible, but it is far harder to achiever compared to the stuff that HAS been demonstrated on mice.

I am PhD in Bio, have an extensive experience with stem cells and gene editing. The idea of human/animal cognitive enhancement is great, but the delivery of gene therapy to adult brains is doomed: first, it's technically challenging if not impossible, second, if we want to achieve a true revolution in cognition, we need to target brain development not already developed brai... (read more)

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3GeneSmith
Has anyone done 2500 edits in the brain cells of an animal? No. The graphs are meant to illustrate the potential of editing to affect IQ given a certain set of assumptions. I think there are still significant barriers that must be overcome. But like... the trend here is pretty obvious. Look at how much editors have improved in just the last 5 years. Look at how much better our predictors have gotten. It's fairly clear where we are headed. Also, to say that none of this stuff has been done in animals seems a bit misleading. Here's a paper where the authors were able to make a desired edit in 60% of mouse brain cells. Granted, they were using AAVs, but for some oligogenic conditions that may be sufficient; you can pack a single AAV with a plasmid holding DNA sufficient to make sgRNA for 31 loci using base editors. There are several conditions for which 30 edits would be sufficient to result in a >50% reduction in disease risk even after taking into account uncertanties about which allele is causal. Granted, if we can't improve editing efficiency in neurons to above 5% then the effect will be significantly reduced. I guess I am fairly optimistic on this front: if an allele is having an effect in brains, it seems reasonable to assume that some portion of the time it will not be methylated or wrapped around a histone, and thus be amenable to editing. Regarding lipid nanoparticles as a delivery vehicle for editors: Verve-101 is a clinical trial underway right now evaluating safety and efficacy of lipid nanoparticles with a base editor to target PCSK9 mutations causing familial hypercholesterolemia. There are other links in the post such as one showing transcytosis of BBB endothelial cells using angiopep conjugated LNPs. And here's a study showing about 50% transfection efficiency of LNPs to brain cells following intracranial injection in mice. Technically challenging? Yes. Impossible? Obviously not. You can get payloads into the brain. You can make edits in cells.