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Prototype follows the story of Alex Mercer, an amnesia-stricken experiment. As the game begins Alex finds himself on the experimentation table with absolutely no memory of his past. The bewildered prototype emerges from an underground lab far below the heart of New York City, only to realize that there is a lot more going on in the outside world.

Prototype's gameplay is centred around Alex's superhuman powers. He has superhuman speed, strength, and toughness, as well as the abilities of consuming his fallen enemies, shapeshifting his body, and easily manoeuvring in the New York City environment. The developers claim that there will be 750 different "unique combinations" of abilities.