Saporin as a Commercial Reagent: Its Uses and Unexpected Impacts in the Biological Sciences—Tools from the Plant Kingdom

Abstract

Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed ‘molecular surgery’, with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer’s Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.

Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage

“…Saporin is a potent and highly useful cell-killing agent for the development of IT therapies. Useful features of saporin include low cytotoxicity when not internalized (it lacks a cell-binding domain), strong cell-killing activity once internalized, molecular stability, resistance to chemical procedures, and the potential to produce saporin-ITs in yeast [ 52 , 53 ]. Consistent with our study, a previous study demonstrated that CD3-saporin is highly efficient in inducing cell death [ 96 ].…”

“…We created a new murine CD3e IT (S-CD3e-IT) using the streptavidin–saporin (sZAP) conjugation system and analyzed saporin-induced VLS as a model protein toxin. Saporin toxins have been increasingly used in recent in vivo animal studies [ 52 , 53 ]. However, to date, the causal effects of saporin on VLS remain poorly investigated and somewhat controversial [ 54 , 55 , 56 ].…”

Quantum Dot-Based Screening Identifies F3 Peptide and Reveals Cell Surface Nucleolin as a Therapeutic Target for Rhabdomyosarcoma

“…To assess the ability of the selected peptides to bind, internalize, and deliver a payload in the cytoplasm in RMS cells, we conjugated biotinylated peptides to the commercially available Streptavidin-ZAP, consisting of Saporin chemically conjugated to Streptavidin ( Figure 4 a). Saporin is a ribosome-inactivating protein first isolated from Sapinaria officinalis [ 49 ], which is useful to evaluate immunotoxin strategies and to delete specific cells in vivo [ 50 ]. Saporin depurinates a specific nucleotide in the ribosomal RNA 28S (A 4324 ), thus irreversibly blocking protein synthesis.…”

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

“…The ‘Molecular Surgery’ technique [ 12 ] requires a targeting agent to specifically bind to a cell-surface molecule on the appropriate cell population. Specificity is usually provided by the targeting agent to a target.…”

“…ATS was established to meet and augment the demand for targeted toxins. In the beginning, the market consisted mostly of neuroscientists who wanted to study specifically-lesioned neurons; these immunotoxins were appreciated and created new techniques, new careers, and new discoveries [ 12 ].…”