Targeting Talk: Safety of the Toxin

Q: Our QA group wants to know about the safety of the toxin in your conjugates? What precautions should we take in handling saporin products?

A: Saporin is a Type 1 ribosome-inactivating protein (RIP), due to its N-glycosidase activity, from the seeds of Saponaria officinalis. It was first described by Fiorenzo Stirpe and his colleagues in 1983 in an article that illustrated the unusual stability of the protein.[1] Among the RIPs are some of the most toxic molecules known, including ricin and abrin (the latter is the poison preferred by the characters in movie The Blue Lagoon). These toxins contain a second protein strand that inserts the RIP into a cell, making it able to enzymatically inactivate the ribosomes, shutting down protein synthesis and resulting in cell death, and eventually causing death of the victim.

Saporin does not possess a cell-binding chain[2] and has no method of internalization without a targeting agent to escort it into a cell. It is this fact that also adds to the safety of its use in the lab. Autoclaving or exposure to 0.2 M NaOH is sufficient to decontaminate material that has been in contact with Saporin and its conjugates. The LD50 for Saporin in mice is 4-8 mg/kg;[3] this dosage amount would be insignificant in humans. Hundreds of articles in the scientific literature (search “Saporin” in Pub Med) have demonstrated tremendous specificity in targeting neuronal cells with many different Saporin conjugates and by many different scientists.

REFERENCES

  1. Stirpe F, Gasperi-Campani A, Barbieri L, Falasca A, Abbondanza A, Stevens WA. (1983). Ribosome-inactivating proteins from the seeds of Saponaria officinalis L. (soapwort) of Agrostemma githago L. (corn cockle) and of Asparagus officinalis (asparagus) and from the latex of Hura crepitans L. (sandbox tree). Biochem J 216(3): 617–625. PMID 6667259
  2. Barthelemy I, Martineau D, Ong M, Matsunami R, Ling N, Benatti L, Cavallaro U, Soria M, Lappi DA. The expression of saporin, a ribosome-inactivating protein from the plant Saponaria officinalis, in Escherichia coli. J Biol Chem. 1993;268(9):6541-8. PMID: 8454624.
  3. Stirpe F, Derenzini M, Barbieri L, Farabegoli F, Brown AN, Knowles PP, Thorpe PE. Hepatotoxicity of immunotoxins made with saporin, a ribosome-inactivating protein from Saponaria officinalis. Virchows Arch B Cell Pathol Incl Mol Pathol. 1987;53(5):259-71. PMID: 2889289.