The movie begins with an explanation of the technology of CRISPR in 1993, which is used for dangerous experiments. We are then taken to present day, where on a space station, a lab rat has been mutated and slaughtered the whole crew. The lone survivor, Kerry Atkins, contacts the corporation she works for, Energyne, who is also responsible for the CRISPR mutations, in hopes they’ll assist her. The corporation’s CEO, Claire Wyden to retrieve the samples that had used or to not return at all. Kerry manages to acquire the samples while avoiding the monster rat, but as she attempts to leave the station in an escape pod, it breaks and explodes, killing her and scattering the samples across the United States in the process.
In San Diego at an animal sanctuary, a primatologist by the name Davis Okoye, along with his co-workers, Amy, Conner, and Nelson, traverse through an ape enclosure. Inside, they witness an ape named Pavo attempting to find a mate before Davis splits them up and talks down an upset Pavo. An albino gorilla by the name of George then appears, frightening Conner, which upsets Pavo, who charges only to be knocked down by George, who we discover to be very playful.
That night, the mutagen samples crash land, one in George’s enclosure, another in a forest, and one in a river in Florida. While George and a lone wolf are sprayed with their contents, a crocodile eats the entire sample. The next morning, when Davis comes in to check on George, he is informed that he is in the bear enclosure. He finds him with a dead bear and George hiding with scratch marks, indicating that the bear attacked him first. The ape comes out, revealing he is now nine feet tall.
News reports about the mutagen landings begin to pop up, with a woman named Kate Caldwell,as well as Claire Wyden and her brother Brett Wyden seeing the reports, with Claire stating that the “Project Rampage” experiment is a success. In an attempt retrieve the mutagen samples, Claire suggest sending a private military group.
Kate arrives at the animal sanctuary, trying to talk with Davis about what is happening to George, claiming that she had worked for Energyne, having created the mutagen, so she would know how to fix George. But starts to grow more aggressive, breaking out of his cage and running rampant through the sanctuary. As the police arrive, Davis attempts to talk him down until a helicopter flies in, shooting George with tranquilizer darts until he is unconscious.
In Wyoming, the military group arrives to acquire the samples that had landed there, but as they traverse deeper, they instead find the canister empty, dead wolves, and an enormous paw print in the ground. Very soon, they attacked by the massive mutated wolf, later nicknamed Ralph. They all attempt to shoot him down, but have no effect on him as he quickly eliminates them one by one. Their helicopter is taken out as well as Ralph leaps through the trees and destroys it.
At the animal sanctuary, a government agent by the name of Harvey Russell arrives, taking George onto a plane and taking Davis and Kate for questioning. As they fly, Russell tells them that he’d looked through their records, revealing that Kate was fired from Energyne for trying to steal research from their labs, and spent 13 months in prison. Davis soon realizes that she had lied to him and cannot fix George.
Soon after the incident with Ralph, Claire activates a radio frequency that will draw in the mutated animals to the Energyne building in Chicago. Ralph and the crocodile, nicknamed Lizzie, immediately make their way there, while on the plane, George begins to wake up from his sedatives. He then attempts to free himself, breaking out of his cage and attacking multiple agents on the plane. He almost kills Russell until Davis manages to intervene enough so that he only knocks him out. As the plane begins to descend into a crash, Davis straps parachutes on to Kate, Russell, and himself before ejecting them out as the plane crashes.
The three of them land and found out that George had survived the crash and on his way to Chicago. Davis explains to Kate that he no longer trusts her, causing her to explain that when she had worked at Energyne, her brother developed cancer, prompting her to use CRISPR to help him. But she soon learned that Claire was using CRISPR to develop dangerous experiments. She tried to get away with research, but was caught and put in jail. Russell soon awakens afterwards and decides to help the two.
George, Ralph, and Lizzie