Massive and accurate mass genome editing for enabling scalable rejuvenation

[LifeIsStrange]

Accurate methods usually are single base and classic methods including most crisprs are low throughput, costly because of bad penetrance and mutagenic /immunogenic.
https://x.com/pdhsu/status/1971293821418995988
and other new methods might make my original dream a reality.

[LifeIsStrange]

Feed https://www.google.com/search?q=megabase+DNA+editing+pubmed&oq=megabase+DNA+editing+pubmed+&gs_lcrp=EgZjaHJvbWUyBggAEEUYOTIHCAEQIRigATIHCAIQIRigATIHCAMQIRigAdIBCTEwNjk3ajBqNKgCALACAA&sourceid=chrome-mobile&ie=UTF-8

The key question being what are the efficiency, specificity and cost.

[LifeIsStrange]

Average gene size is 10-15kb, highest is 2.5mb
However if subpatterning is possible beyond single base editing then in practice we would probably be fine with 100b accurate editing we could even go very far with 10 or 1b

[LifeIsStrange]

Potentially mutagenesis free method |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
https://www.nature.com/articles/s41467-025-56734-9

Massive editing at 95% accuracy????
https://www.embopress.org/doi/full/10.1038/s44319-024-00364-7

Programmable
https://www.science.org/doi/abs/10.1126/science.adt5199

50% efficiency
https://www.nature.com/articles/s41467-023-39137-6

[LifeIsStrange]

80%? https://x.com/zhaoweiasu/status/1957990451518247322

[LifeIsStrange]

https://pubmed.ncbi.nlm.nih.gov/40014809/
Let's review the actual blockers for mass democratization of even single base

Smallest editors
https://www.mdpi.com/1422-0067/26/5/2357

Can't we split them and recombine them within cells?
Cf magic bullet and moiety research

Single aav limit is 4.7kb but dual aav exist.
Also for aav free, split editors are being researched?

[LifeIsStrange]

Very high editing efficiency from reinforced lipids
https://pubmed.ncbi.nlm.nih.gov/41004579/

[LifeIsStrange]

https://substack.com/@asimovpress/note/c-162944306