To be directed by "Cypher" and "Getting Gilliam" director Vincenzo Natali, the film will explore a dark side of genetic engineering.
Polley and Brody will play scientists who become famous for splicing different animal DNA to create new creatures, ultimately daring to cross legal and ethical boundaries to introduce human genes into their experiments, the trade paper said.
The screenplay was written by Natali, Antoinette Terry Bryant and Doug Taylor.
Polley will soon be seen in the HBO "John Adams" miniseries. She also recently earned critical acclaim for directing the drama "Away From Her."
Brody, who won an Oscar for "The Pianist," can be seen in "The Darjeeling Limited."
Shooting on "Splice" is to begin next month in Toronto.