References

Su Y, Xu J, Zhu Z, Chin J, Xu L, Yu H, Nudell V, Dash B, Moya EA, Ye L, Nimmerjahn A, Sun X (2024) Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity. Nature 631(8021):601-609. doi: 10.1038/s41586-024-07608-5 PMID: 38987587

Objective: To map a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner.

Summary: Ablation or chemogenetic inactivation of Dbh+nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+nTS neurons project to the nucleus ambiguous (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+nTS and NA.

Usage: To determine whether Dbh+nTS neurons are essential for hyperreactivity chemical ablation, anti-dopamine beta-hydroxylase antibody conjugated to saporin (Anti-DBH-SAP, IT-03), shown to be specific for DBH+neurons, was injected into the nTS.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Bryder D, Konturk-Ciesla A, Zhang Q, Kharazi S (2024) A non-invasive stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Research Square doi: 10.21203/rs.3.rs-4528815/v1

Objective: To develop a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated Hematopoietic stem cell.

Summary: Authors demonstrate that young HSCs, once transplanted, survive and thrive in aged hosts, dramatically improving hematopoietic output and ameliorating age-compromised lymphopoiesis.

Usage: Intravenous injection of CD45-SAP (3 mg/kg, IT-91). Biotinylated anti-CD45.2 antibodies were mixed with streptavidin-saporin conjugate at a 1:1 molar ratio (IT-27).

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)

Xia L, Luo L, Liu J, Liu L, Han H, Xia R, Guo L, Xie J, Tang L (2024) A glycoprotein-based surface-enhanced raman spectroscopy–lateral flow assay method for abrin and ricin detection. Toxins (Basel) 16(7):312. doi: 10.3390/toxins16070312 PMID: 39057952

Objective: To generate stable and high-affinity nanotags, via an efficient freezing method, to serve as the capture module for surface-enhanced Raman spectroscopy (SERS) and lateral flow assay (LFA) (SERS-LFA).

Summary: The detection method demonstrated good inter-batch and intra-batch reproducibility among the test strips, and the detection could be completed within 15 min, indicating the suitability of this SERS-LFA method for the on-site rapid detection of abrin and ricin toxins.

Usage: The specificity of the test strip for abrin was assessed against RCA120, AAG, RTB, RTA, Stx1, Stx2, saporin, and SEB. Proteins, such as RTA, Stx 1, Stx 2,saporin, and SEB, did not cross-react with this assay.

Related Products: Saporin (Cat. #PR-01)

Kolster M, Sonntag A, Weise C, Correa J, Fuchs H, Walther W, Fernandez-Megia E, Weng A (2024) Broadening the scope of sapofection: Cationic peptide-saponin conjugates improve gene delivery in vitro and in vivo. ACS Appl Mater Interfaces doi: 10.1021/acsami.4c05846 PMID: 38970470

Objective: Using Saponin to enhance delivery of gene therapies to cancer cells

Summary: Saponins hold promise in enhancing the endosomal escape of gene therapy vectors into cells, thereby increasing efficacy. The Saponin, SO1861, was conjugated to either a pH-sensitive peptide linker or Saporin, and internalization of the payload was measured. Saponin was shown to enhance delivery of gene therapies to cells of an aggressively growing neuroblastoma allograft model in mice.

Related Products: Saporin (Cat. #PR-01)

Branco F, Cunha J, Mendes M, Vitorino C, Sousa JJ (2024) Peptide-hitchhiking for the development of nanosystems in glioblastoma. ACS Nano 18(26):16359-16394. doi: 10.1021/acsnano.4c01790 PMID: 38861272

Objective: To review single and multiligand strategies to deliver therapeutic treatment to Glioblastoma (GBM).

Summary: The exploration of multitargeting ligands has shown great promise in GBM treatment, particularly when compared to single-targeting approaches. These ligands simultaneously use different peptides to engage a range of overexpressed receptors. These advanced strategies enhance the precision of drug delivery, facilitate BBB penetration, and enable targeting specific molecular pathways within the complex microenvironment of GBM.

Usage: ApoE-modified saporin-loaded chimeric polymersomes showed a highly efficient crossing of the BBB and accumulation in GBM.

Related Products: Saporin (Cat. #PR-01)

Ciuro M, Sangiorgio M, Cacciato V, Cantone G, Fichera C, Salvatorelli L, Magro G, Leanza G, Vecchio M, Valle MS, Gulino R (2024) Mitigating the functional deficit after neurotoxic motoneuronal loss by an inhibitor of mitochondrial fission. Int J Mol Sci 25(13):7059. doi: 10.3390/ijms25137059 PMID: 39000168

Objective: To use the Cholera Toxin B-Saporin (CTB-SAP) mouse animal model of Amyotrophic lateral sclerosis (ALS) to determine the efficacy of mitochondrial division inhibitor 1 (Mdivi-1) for its potential neuroprotective effect.

Summary: Mdivi-1 reduced motor deficits in the ALS model. It also showed neuroprotective effects on motoneurons and promoted plasticity. This could represent a translational approach for motoneuron disorders.

Usage: To establish the model, mice received two injections of the retrogradely transported, ribosome-inactivating toxin, CTB-SAP (Cat. #IT-14) into the medial and lateral right gastrocnemius muscles, respectively, with a toxin dose of 6 μg/2 μL in PBS per injection.

Related Products: CTB-SAP (Cat. #IT-14)

Kang Y, Toyoda H, Saito M (2024) Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer’s disease. Front Cell Neurosci 18:1425645. doi: 10.3389/fncel.2024.1425645 PMID: 38994328

Summary: It remains unclear how masticatory dysfunction can induce brain degeneration similar to Alzheimer’s Disease (AD), and the neural mechanism linking the trigeminal nervous system responsible for mastication and the cognitive and memory brain system remains unknown. In this review paper, authors provide clues to the search for such “missing link” by discussing the embryological, anatomical, and physiological relationship between locus coeruleus (LC) and its laterally adjoining mesencephalic trigeminal nucleus which plays a central role in the masticatory functions.

Usage: To clarify the role of BFC neurons such as in nucleus basalis of Meyner (NBM) in AD pathogenesis, selective lesioning of basal forebrain cholinergic (BFC) neurons was made using the immunotoxin mu p75-SAP (IT-16) in such transgenic mice. The lesioning of BFC neurons resulted in an earlier appearance of Aβ accumulation and memory impairment in the cortex and hippocampus.

Related Products: mu p75-SAP (Cat. #IT-16)

See Also:

• Laursen B et al. Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice. Behav Brain Res 240:146-152, 2013.
• Ramos-Rodriguez JJ et al. Rapid beta-amyloid deposition and cognitive impairment after cholinergic denervation in app/ps1 mice. J Neuropathol Exp Neurol 72(4):272-285, 2013.

Kumawat C, Takahashi T, Date I, Tomita Y, Tanaka M, Arataki S, Komatsubara T, Flores AOP, Yu D, Jain M (2024) State-of-the-art and new treatment approaches for spinal cord tumors. Cancers (Basel) 16(13):2360. doi: 10.3390/cancers16132360 PMID: 39001422

Objective: To discuss innovative approaches in treating spinal cord tumors.

Summary: Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body’s own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach.

Usage: A notable study by Yan et al. involved a novel bone-targeted protein nanomedicine that combines saporin with a boronated polymer, encapsulated in an anionic poly (aspartic acid) layer. In mouse models, these nanoparticles accumulated in the bone and released saporin in response to the acidic tumor environment, effectively inactivating ribosomes and inducing cancer cell death.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Yan Y et al. Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors. Bioact Mater 7:333-340, 2021.

Garaudé S (2024) Engineering an antibody-discernible and functional CD45 variant on hematopoietic stem and progenitor cells via base editing. Univ Basel Thesis.

Objective: To develop a system for a cell surface marker present on all hematopoietic cell to deplete malignant cells. Authors screened CD45’s extracellular domain regions with base editors and generated multiple CD45 protein variants altering the binding of antibodies.

Summary: Authors selected the CD45 K352E/G variant profile and improved its base editing rate as it showcased loss of binding of a unique anti-CD45 antibody while still maintaining the surface marker’s expression, stability, and function in human hematopoietic stem and progenitor cells (HSPCs). The resulting loss of antibody binding prompted the modification and humanization of the anti-CD45 antibody, culminating in the development of an anti-CD45 antibody-drug conjugate (CD45-ADC; CIM053-SG3376). In an AML mouse models xenografted with HSPCs, administration of the CD45-ADC selectively depleted human leukemia and HSPCs wt cells while preserving the healthy hematopoietic system derived from the transplanted base edited HSPCs.

Usage: In vitro antibody-drug-conjugate (ADC) mediated killing assays. For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody and Streptavidin-ZAP at a 1:1 molar ratio for 30 min at room temperature

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)

Kiyokawa Y, Ootaki M, Kambe Y, Tanaka KD, Kimura G, Tanikawa T, Takeuchi Y (2024) Approach/avoidance behavior to novel objects is correlated with the serotonergic and dopaminergic systems in the brown rat (rattus norvegicus). Neuroscience 549:110-120. doi: 10.1016/j.neuroscience.2024.05.003 PMID: 38723837

Objective: To compare the dopaminergic, serotonergic, and noradrenergic systems immunohistochemically among rats.

Summary: The serotonergic system suppresses avoidance behavior, while the dopaminergic system enhances approach behavior to novel objects.

Usage: Immunohistochemistry (1:5000) Anti‐CRH antibody (AB‐02).

Related Products: Corticotropin Releasing Hormone Rabbit Polyclonal (Cat. #AB-02)