Ranpirnase

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 and antiviral treatment due to its unusual mechanism of cytotoxicity tested against transformed cells and antiviral activity.[2]

Ranpirnase
Crystallographic structure of ranpirnase in complex with RNA.[1]
Identifiers
OrganismRana pipiens
Symboln/a
PDB2I5S
UniProtP85073
Other data
EC number3.1.27

Ranpirnase was originally discovered by scientists at TamirBio[3], a biotechnology company (formerly Alfacell Corporation), where it was tested in preclinical assays[4] and in clinical trials under the name Pannon or Onconase, and TMR004. The mechanism of action of ranpirnase has been attributed to the RNA interference pathway, potentially through cleaving siRNA molecules;[5] to cleavage of transfer RNA;[2] and to interference with the NF-κB pathway.[6] Currently (as of March 2020) Ranpirnase is in clinical trials as a potential antiviral.[7]

References
  1. Lee JE, Bae E, Bingman CA, Phillips GN, Raines RT (January 2008). "Structural basis for catalysis by onconase". Journal of Molecular Biology. 375 (1): 165–77. doi:10.1016/j.jmb.2007.09.089. PMC 2151974. PMID 18001769.
  2. Ardelt W, Shogen K, Darzynkiewicz Z (June 2008). "Onconase and amphinase, the antitumor ribonucleases from Rana pipiens oocytes". Current Pharmaceutical Biotechnology. 9 (3): 215–25. doi:10.2174/138920108784567245. PMC 2586917. PMID 18673287.
  3. https://www.fiercebiotech.com/biotech/tamir-reports-positive-effect-against-sars-virus
  4. Darzynkiewicz Z, Carter SP, Mikulski SM, Ardelt WJ, Shogen K (May 1988). "Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent". Cell and Tissue Kinetics. 21 (3): 169–82. doi:10.1111/j.1365-2184.1988.tb00855.x. PMID 3224365.
  5. Zhao H, Ardelt B, Ardelt W, Shogen K, Darzynkiewicz Z (October 2008). "The cytotoxic ribonuclease onconase targets RNA interference (siRNA)". Cell Cycle. 7 (20): 3258–61. doi:10.4161/cc.7.20.6855. PMC 2586937. PMID 18927512.
  6. Nasu M, Carbone M, Gaudino G, Ly BH, Bertino P, Shimizu D, Morris P, Pass HI, Yang H (May 2011). "Ranpirnase Interferes with NF-κB Pathway and MMP9 Activity, Inhibiting Malignant Mesothelioma Cell Invasiveness and Xenograft Growth". Genes & Cancer. 2 (5): 576–84. doi:10.1177/1947601911412375. PMC 3161417. PMID 21901170.
  7. Clinical trial number NCT03856645 for "OKG-0301 for the Treatment of Acute Adenoviral Conjunctivitis (RUBY)" at ClinicalTrials.gov

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