targeted-toxins

Luna-Munguia H, Gasca-Martinez D, Garay-Cortes A, Coutiño D, Regalado M, de Los Rios E, Villaseñor P, Hidalgo-Flores F, Flores-Guapo K, Benito BY, Concha L (2024) Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus. Mol Neurobiol 61(10):1-21. doi: 10.1007/s12035-024-04069-9 PMID: 38443731

Objective: To evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus.

Summary: Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Regarding the pilocarpine-induced status epilepticus, an increased mortality rate was observed. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.

Usage: Injection of 192-IgG-SAP (375 ng/μl dissolved in sterile 0.1X PBS) and GAT1-SAP (325 ng/μl dissolved in sterile 0.1X PBS) into the MS to selectively target choline neuron or GABA populations of the medial septum, respectively.

Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-01)

Kitawi R, Ledger S, Kelleher AD, Ahlenstiel CL (2024) Advances in HIV gene therapy. Int J Mol Sci 25(5):2771. doi: 10.3390/ijms25052771 PMID: 38474018

Objective: This review highlights the various stages of ex vivo gene therapy, current research developments that have increased the efficiency and safety of this process, and a comprehensive summary of Human Immunodeficiency Virus (HIV) gene therapy studies, the majority of which have employed the ex vivo approach.

Summary: The long-term or permanent expression of anti-HIV genes and the modification of CD4+ and CD34+ cells to render them resistant to infection or to allow the disruption of the HIV life cycle are important strategies in the quest to achieve a HIV cure.

Usage: Authors referenced CD117 antibody conjugated to saporin via streptavidin (IT-27, IT-83), which enabled >99% depletion of endogenous HSCs in NSG mice and non-human primates.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

See Also:

• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.

Díaz-Jara E, Pereyra K, Vicencio S, Olesen MA, Schwarz KG, Toledo C, Díaz HS, Quintanilla RA, Del Rio R (2024) Superoxide dismutase 2 deficiency is associated with enhanced central chemoreception in mice: Implications for breathing regulation. Redix Biol 69:102992. doi: 10.1016/j.redox.2023.102992 PMID: 38142585

Objective: To determine the impact of partial deletion of SOD2 expression on (1) O2.−accumulation in the Retrotrapezoid nucleus (RTN), (2) central ventilatory chemoreflex function, and (3) disordered-breathing as well as cellular localization of SOD2 in the RTN of healthy mice.

Summary: Results showed that SOD2+/− mice displayed reductions in SOD2 levels and high O2-formation and mitochondrial dysfunction within the RTN compared to wild type. Additionally, SOD2+/−mice displayed a heightened ventilatory response to hypercapnia and exhibited overt signs of altered breathing patterns.

Usage: Recent research has shown that removing some RTN chemoreceptor neurons using substance P-conjugated saporin toxin can normalize central chemoreflex and respiratory disorders in animals with heart disease, highlighting the significance of RTN neurons in the pathological process of central chemoreflex potentiation.

Related Products: SP-SAP (Cat. #IT-07)

Loftén A, Cadeddu D, Danielsson K, Stomberg R, Adermark L, Söderpalm B, Ericson M (2024) Reduced alcohol consumption following ablation of cholinergic interneurons in the nucleus accumbens of wistar rats. Addict Biol 30(2):e70022. doi: 10.1111/adb.70022 PMID: 39936333

Objective: The aim of this study was to explore the functional role of accumbal Cholinergic interneurons (CIN) in alcohol-related behavior.

Summary: Rats with depleted CIN consumed significantly less alcohol than sham-treated controls. No differences in sucrose preference, motor activity, water intake or weight gain were noted between treatment groups, suggesting that the ablation selectively affected alcohol-related behavior. In conclusion, this study further supports a role for accumbal CIN in regulating alcohol-consummatory behavior.

Usage: Ablation of CIN was induced by local administration of Anti-ChAT-SAP (Cat #IT-42) bilaterally into the nucleus accumbens of male Wistar rats. Dose: 0.5 and 0.75 μg/ul.

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Su Y, Xu J, Zhu Z, Chin J, Xu L, Yu H, Nudell V, Dash B, Moya EA, Ye L, Nammerjahn A, Sun X (2024) Brainstem DBH+ neurons control chronic allergen-induced airway hyperreactivity. bioRxiv 2023.02.04.527145. doi: 10.1101/2023.02.04.527145 PMID: 36778350

Summary: The authors show that a single population of Dbh+ neurons in the nucleus of the solitary tract (nTS) of the brainstem, and downstream neurons in the nucleus ambiguous (NA), are both necessary and sufficient for chronic allergen-induced airway hyperreactivity. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity. This opens the possibility of targeted neural modulation as an approach to control refractory allergen- induced airway constriction.

Usage: Anti-DBH-SAP (IT-03) was injected stereotactically into both sides of the nTS of wild-type mice (42 ng/200 nL). Blank-SAP (IT-21) was used as control.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Blank-SAP (Cat. #IT-21)

Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP (2024) Streptavidin-drug conjugates streamline optimization of antibody-based conditioning for hematopoietic stem cell transplantation. bioRxiv 2024.02.12.579199. doi: 10.1101/2024.02.12.579199 PMID: 38405731

Objective: Use biotinylated CD45.2 antibodies conjugated to Streptavidin to target hematopoietic stem cells (HSCs) for HSC transplantation.

Summary: Hematopoietic stem cell transplantation offers a promising alternative to standard cancer treatments. Using Click Chemistry, different toxic payloads were attached to streptavidin and observed.

Usage: 75 micrograms of CD45.2 delivered to HSCs deriving from B6 mice.

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

Abdolvahab MH, Karimi P, Mohajeri N, Abedini M, Zare H (2024) Targeted drug delivery using nanobodies to deliver effective molecules to breast cancer cells: The most attractive application of nanobodies. Cancer Cell Int 24(1):67. doi: 10.1186/s12935-024-03259-8 PMID: 38341580

Objective: Using nanobodies to deliver saporin to breast cancer cells.

Summary: Through the binding of saporin to a nanobody, a fragment of an antibody, breast cancer cells that over-express Her2 can be targeted and eliminated. Binding of saporin in nanoparticles to 11A4 nanobody (anti-HER2 receptor) showed dose-dependent cytotoxicity against SK-BR-3 cells when tested. Photochemical internalization of saporin loaded nanoparticles also demonstrated dose-dependent cytotoxicty in SK-BR-3 breast cancer cells.

Related Products: Trastuzumab (Anti-HER2)-SAP (Cat. #IT-95)

See Also:

• Martínez-Jothar L, Beztsinna N, van Nostrum CF, Hennink WE, Oliveira S (2019) Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination with Photochemical Internalization. Mol Pharm 16(4):1633-1647. doi: 10.1021/acs.molpharmaceut.8b01318 PMID: 30817164

Aerts EG, Griesgraber MJ, Shuping SL, Bowdridge EC, Hardy SL, Goodman RL, Nestor CC, Hileman SM (2024) The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287. doi: 10.1093/biolre/ioad147 PMID: 37930247

Objective: To investigate the role of NKB-SAP (NK3-SAP) in the arcuate nucleus on the timing of puberty, the LH surge, and the response to the NK3R agonist senktide in female sheep.

Summary: This study explores how the ablation of NK3R-containing neurons in the arcuate nucleus affects puberty onset and reproductive hormone dynamics in female sheep. The findings demonstrate that NK3-SAP injections significantly delay puberty, reduce the amplitude of the LH surge, and alter the response to senktide, underscoring the critical role of NK3R-containing neurons in reproductive function.

Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Martínez-Gardeazabal J, Moreno-Rodríguez M, Llorente-Ovejero A, González de San Román E, Lombardero L, Bengoetxea de Tena I, Sustacha J, Matute C (2024) Cell lipotypes localization in brain by mass spectrometry imaging. bioRxiv 2024.02.02.578599. doi: 10.1101/2024.02.02.578599

Objective: Characterizing the type of different central nervous system cells via mass spectrometry of their component lipids.

Summary: Different varieties of cells in the central nervous system perform different functions and, as a consequence, have different compositions. Using purified rat cell cultures of neurons, astrocytes, oligodendrocytes, microglia, and choroid plexus cells, a model was constructed to identify the localization of any brain cell through mass spectrum imaging of the lipid composition.

Usage: Injected 192-IgG-SAP (130 ng/µl) into the nucleus basalis magnocellularis (nbM) of rats.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Schwarz KG, Pereyra KV, Diaz-Jara E, Vicencio SC, Del Rio R (2025) Brainstem C1 neurons mediate heart failure decompensation and mortality during acute salt loading. Cardiovascular Research 121(2):241-253. doi: 10.1093/cvr/cvae261 PMID: 39775485

Objective: To test whether rostral ventrolateral medulla (RVLM) C1 neurons drive cardiorespiratory decompensation, and ultimately lead to sudden death in heart failure (HF) rats.

Summary: The results strongly suggest that RVLM C1 neurons contribute to acute HF decompensation during salt loading by a mechanism encompassing further increases in sympathetic outflow and hypoxia-related breathing disorder.

Usage: Bilateral injections of anti-dopamine-β-hydroxylase conjugated with saporin toxin (Anti-DBH-SAP; 7.5 ng/100 nl of sterile saline solution) were delivered to the RVLM-C1 region using the stereotaxic coordinates.

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