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Skibidi vibes in the lab as PEI hits the scene, a cationic polymer ready to goon with gene delivery. Lowkey, it has been around since 1995, flexing in basic research but struggling to edge into clinical use. This review dives into the dank details of how PEI works, breaking down cellular uptake and its journey to the nucleus. Major obstacles like toxicity are addressed, pushing for sigma solutions. In vivo, PEI is a mixed bag, with localized delivery getting some love while systemic routes are a challenge. The future is bright for PEI derivatives, ready to ship into new therapeutic realms.