A research space station, Athena-1, owned by gene manipulation company Energyne, is destroyed after a laboratory rat mutates and wrecks havoc. A crew member, Dr Kerry Atkins, is ordered to retrieve research canisters containing a pathogen by CEO Claire Wyden. Atkins is able to flee in the escape pod, but it disintegrates upon reentry, killing her and leaving a trail of debris across the United States, including the Everglades, where a canister is consumed by a crocodile, and a forest in Wyoming, where a wolf is exposed to the pathogen.

Primatologist Davis Okoye, a former US military soldier and member of an anti-poaching unit, is a primatologist in a San Diego wildlife preserve. He befriends a rare albino gorilla named George, whom he saved from poachers. One night, as Davis drives home from work at the San Diego Zoo, part of the debris crashes in George's habitat. George is exposed to the pathogen when he checks it out.

Davis is informed that George is suddenly aggressive, having killed a grizzly bear, and is growing noticeably bigger. He is contacted by Dr. Kate Caldwell, a genetic engineer who explains that this gas was developed by Energyne to rewrite genes on a massive scale. She had hoped to advance CRISPR research as a potential cure for disease, but discovered that Energyne planned to use it as a biological weapon. The company fired her and sent her to prison for attempting to expose them. George is captured by a government team led by Agent Harvey Russell, and is put on a plane. Meanwhile, Claire and her brother Brett send a squad of mercenaries led by Burke to capture the mutated wolf, Ralph, but they are all killed.

The animals having been engineered to respond aggressively to a certain sound frequency, Claire uses a massive transmitter to lure Ralph to Chicago so they can not only capture it, but use it to have George kill Kate to cover up their true intentions. George reacts violently to the sound and crashes the plane. Davis saves Kate and Agent Russell from the plane before it explodes. George, who also survived, "joins forces" with Ralph as they make their way to Chicago. Davis and Kate convince Russell to help them steal a helicopter so they can get ahead of George.

By the time they arrive, George and Ralph are attacking the city. The military are overwhelmed when a mutated crocodile, Lizzie, arrives, and causes more casualties. Davis and Kate attempt to steal a serum with the hope they can turn the mutated animals back to normal. They are able to reach Energyne and steal a handful of serums, but are caught by Claire and Brett. Claire reveals that the serum only eliminates the animals' aggressiveness rather than revert them to their normal sizes, and shoots Davis, though he survives. When George climbs up to the top of the Energyne Building and causes chaos, Claire orders Davis to distract him while she attempts to escape with Kate held at gunpoint. During the escape, Kate slips the cure into Claire's handbag and pushes her towards George, who eats her, and thus the cure, and destroys the transmitter.

With George returned to his normal personality, Davis stays to help him defeat the other two animals while Kate flees to prevent the military from dropping a MOAB bomb on the city. Russell is able to take a laptop of incriminating evidence from Brett before the latter is crushed by falling rubble. George and Davis are able to kill Ralph by tricking him into flying between Lizzie's jaws, while George kills Lizzie by impaling her with a metal bar. With the threat neutralized, the airstrike is called off and George helps in clearing the city of debris.

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