CRISPR editing needs the Cas9 protein and its guide RNA delivered
across the plasma membrane, out of the endosome, and into the nucleus
before it degrades. Each carrier trades off packaging capacity,
immune visibility and escape efficiency differently.
P(edit) = P(bind) · P(uptake) · P(endosomal escape) · P(nuclear entry)
- AAV vector — viral capsid, high uptake but can be neutralised by pre-existing antibodies.
- LNP — lipid nanoparticle, good endosomal escape via ionisable lipids, current mRNA-vaccine standard.
- Polymer NP — cheap and tunable, but escape is the weak step.
- Electroporation — physical pulse punches transient membrane pores; near-total uptake, ex vivo only.
- Immune neutralisation — fraction of carriers cleared before they ever reach the membrane.
Turning the endosomal escape barrier off models a physical method
(like electroporation) that bypasses the endosome entirely.