Nuclear Pore Gene-Cargo Transport

Reaching the genome is the last, and often the hardest, step of any non-viral gene therapy: the payload must cross the nuclear envelope through a nuclear pore complex. This simulator models a swarm of gene-therapy cargo — lipid or polymer nanoparticles carrying plasmid DNA, mRNA or a CRISPR ribonucleoprotein — diffusing through the cytoplasm and attempting to cross into the nucleus. Cargo below the ~5 nm passive-diffusion cutoff slips through freely; larger cargo needs nuclear-localization-signal (NLS) copies to engage importin-β and the FG-nucleoporin mesh, and even then transport is gated by the RanGTP gradient that makes the process directional. Tune cargo size, NLS copy number, the RanGTP gradient and pore density, and watch the live nuclear-entry rate track exactly the biology behind why some gene-therapy vectors reach the nucleus efficiently and others stall outside it.