Retro-mutagen is made from regular mutagen, but the source mutagen must undergo complex chemical alterations that involve April O'Neil's DNA. April was herself born a Human-Kraang hybrid mutant, inheriting traits from her mother whose family line had been genetically altered by Kraang experiments. One of April's special properties is an immunity to mutagen itself, which is instrumental to how Donnie's retro-mutagen reverses the effects of mutation. Unlike regular Mutagen which is cyan in color, Donatello's successful batches of Retro-Mutagen are orange in color.