Ranpirnase

2I5S.png Crystallographic structure of ranpirnase in complex with RNA.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Ranpirnase is a ribonuclease enzyme found in the oocytes of the Northern Leopard Frog (Rana pipiens). Ranpirnase is a member of the pancreatic ribonuclease (RNase A) protein superfamily and degrades RNA substrates with a sequence preference for uracil and guanine nucleotides. Along with amphinase, another leopard frog ribonuclease, ranpirnase has been studied as a potential cancer treatment due to its unusual mechanism of cytotoxicity tested against tumor cells.

Ranpirnase was originally discovered by scientists at TamirBio, a biotechnology company (formerly Alfacell Corporation), where it was tested in clinical trials under the brand name Onconase. The mechanism of action of ranpirnase tumor-selective cytotoxicity has been attributed to the RNA interference pathway, potentially through cleaving siRNA molecules; to cleavage of transfer RNA; and to interference with the NF-κB pathway. Despite early indications of promise as a mesothelioma treatment, and an orphan drug status designation from the United States Food and Drug Administration in 2007, the Phase III clinical trial for this indication did not demonstrate statistical significance against primary endpoints.