Noh M, Corrigan KA, Williams SG, Peirs C, Leone MJ, Headrick DJ, Guvercin M, Lee S, Phan BN, Yeramosu D, Babu S, Brown AR, Van De Weerd R, Zhao X, Dunn RP, Mathys H, Pfenning AR, Seal RP (2025) A molecular and spinal circuit basis for the functional segregation of itch and pain. bioRxiv 2025.07.31.667966. doi: 10.1101/2025.07.31.667966
Objective: To define how distinct subtypes of Grpr⁺ dorsal horn neurons contribute to itch and pain processing and to demonstrate the utility of genomic enhancer-based strategies for modality-specific targeting.
Summary: The study revealed two functionally distinct Grpr⁺ neuron subtypes: Tac1⁻ neurons mediate itch, while Tac1⁺ neurons mediate mechanical allodynia. Selective silencing or ablation of each subtype modulated only its respective sensory behavior, illustrating clear modality segregation within the dorsal horn circuitry.
Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally (300 ng) to selectively ablate Grpr⁺ neurons
Windhorst U, Dibaj P (2025) Nociception and acute pain: Neurotransmitters and neuromodulators. Preprints.org preprints202508.0487.v1. doi: 10.20944/preprints202508.0487.v1
Objective: To review the huge variety of additional neurotransmitters, neuromodulators and hormones in the nociceptive and pain system
Summary: Nociception and acute pain are governed by a dynamic interplay of structures and substances, modulated by internal and external factors, and vulnerable to pathological reorganization.
Usage: The injection of anti‐DBH‐SAP induced neurodegeneration restricted to the NA A5 cell group and confirmed by the decrease in the number of NA neurons only in the A5 group.
Nie AA, Taylor BK (2025) The pharmacotherapeutic potential of neuropeptide Y for chronic pain. J Intern Med doi: 10.1111/joim.20118 PMID: 40754889
Objective: To evaluate how neuropeptide Y (NPY) and its receptor subtypes (Y1 and Y2) regulate acute and chronic pain, and to explore the therapeutic potential of targeting these pathways for the treatment of neuropathic and inflammatory pain.
Summary: The review highlights that spinal Y1-interneurons contribute to both sensory and affective components of chronic pain and that Y1 receptor activation can inhibit pronociceptive signaling. Prior studies using NPY-SAP demonstrated that ablation of Y1-expressing neurons reduces hypersensitivity in models of nerve injury and inflammation, supporting Y1 modulation as a therapeutic avenue.
Usage: NPY-SAP (IT-28) was referenced in the context of earlier studies employing intrathecal administration to ablate spinal Y1-interneurons.
Pandala N, De Melo Haefeli L, Lang M, Stone EM, Mullins RF, Tucker BA, Han IC (2025) Development of a targeted choroidal injury model for the study of retinal degenerations and therapeutic cell replacement. bioRxiv 2025.07.29.667466. doi: 10.1101/2025.07.29.667466
Objective: To report a new targeted choroidal injury model using saporin conjugates and compare them to models of systemic sodium iodate administration.
Summary: Suprachoroidal administration of Anti-CD38-SAP or Anti-CD105-SAP resulted in severe choroidal vascular injury localized to the injection site, without damage to adjacent choroidal vasculature, progressive injury over time, or development of choroidal neovascularization. By contrast, sodium iodate treated animals had rapid, diffuse choroidal loss which progressed throughout the study time points, with fatal systemic side effects at the highest (75 mg/kg) dose.
Usage: Anti-CD38-SAP (IT-96) or Anti-CD105-SAP (IT-80) were diluted in sterile PBS at a concentration of 0.05 μg/μl. To induce selective choroidal cell injury, 10μl of saporin conjugate solution was delivered via suprachoroidal injection.
Kofoed C, Erkalo G, Tay NES, Ye X, Lin Y, Muir TW (2025) Programmable protein ligation on cell surfaces. Nature 10.1038/s41586-025-09287-2. doi: 10.1038/s41586-025-09287-2 PMID: 40739351
Objective: To describe an autonomous decision-making device driven by proximity-gated protein trans-splicing that allows local generation of an active protein from two otherwise inactive polypeptide fragments
Summary: Authors showed that this protein-actuator platform can perform convergent protein ligation on designated cell surfaces, allowing highly selective generation of active proteins, which can either remain physically associated with the cell surface on which they were manufactured or be released into the surrounding milieu.
Usage: Flow cytometry: Mixed K562 cells (phenotypes indicated) were treated with a two-dose regimen of SMART-SpyCatcher/SpyTag003-biotin ([HER2 AND EGFR] logic,100 nM each) and Streptavidin–ZAP (20 nM) at a 24-h interval. Cell viability was assessed after 72 h by flow cytometry and normalized to untreated wild-type cells.
We are highlighting one of our saporin conjugates, Bombesin-SAP. A tool for depleting cells that express gastrin releasing peptide receptor (GRPR). Bombesin is a 14-amino acid peptide actually found in frog skin. The human equivalent GRP has been detected in itch pathways and plays a role in eating behaviors.
Their objective was to investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
The authors were able to administer Bombesin-SAP (IT-40) or a control conjugate (Blank-SAP, IT-21) intrathecally to ablate GRPR-positive spinal neurons to assess their role in sensory behavior.
In their study, they identified Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation revealed distinct sensory processing roles for various neuronal subtypes.
Li Y, Liu J, Yao L, Mao T, Wang X, He Z, Lyu J, Wang W (2025) Synergistic effect of guanidinium and tertiary amine groups on boosting gene delivery. JACS Au 5(8):3951-3959. doi: 10.1021/jacsau.5c00592 PMID: 40881396
Objective: To design and develop a new versatile branched poly (β-aminoester) (PAE)-based delivery system by incorporating the synergistic effects of guanidinium and tertiary amine functional groups, resulting in enhanced nucleic acid (DNA/mRNA) delivery.
Summary: The results show that self-assembly occurs when polymers containing different functional groups are mixed, which changes the interactions between molecules and significantly affects the structure of the polyplex. This synergy was found to significantly enhance cellular uptake, contributing to improved transfection efficiency.
Usage: The protein delivery capabilities of these polymers were further evaluated by delivering the toxic protein Saporin (SAP) in HEK cells. The results showed that all polymers were effective, with cell killing rates exceeding 70%; however, no significant differences were observed among the polymers.
Nollet M, Ba W, Soto BA, Yin C, Lignos L, Jovic K, Vyssotski AL, Yustos R, Franks NP, Wisden W (2025) The selective amyloid-driven failure of cholinergic medial septal neurons in aging mice perturbs REM sleep, cognition and emotion, and broadcasts amyloid to other brain regions. bioRxiv 2025.07.09.663930. doi: 10.1101/2025.07.09.663930
Objective: To look genetically at the intersection of amyloid pathology and the cholinergic system in Alzheimer’s disease (AD).
Summary: The broadcasting of amyloid by medial septal cholinergic cells is a notable feature, and potentially important in human pathology, selective genetic lesioning of about one third of the medial septal cholinergic cells, independent of amyloid, gave the same REM sleep, cognitive and emotional phenotypes. Thus, it is the killing of the cholinergic cells by amyloid, and therefore the missing acetylcholine, and not the secreted/deposited amyloid in the hippocampus and other areas, that is the critical feature. These findings underscore the interest in revitalizing the classic cholinergic hypothesis of AD. Restricting pathological amyloid expression to MS cholinergic neurons, so that their health is compromised by amyloid, is sufficient to reproduce many AD-like symptoms, highlighting the critical role of these cells in early AD pathogenesis, REM sleep regulation, emotion and cognition.
Usage: Cholinergic neurons throughout the forebrain in mice were lesioned with mu p75-SAP. The loss of cholinergic innervation exacerbated neurovascular impairments and cerebral amyloid angiopathy progression in the cortex and hippocampus
Peterson D (2025) Alternative treatments and potential cures for type 1 diabetes. SD State Univ Thesis.
Objective: To discuss alternative treatment for type one diabetes.
Summary: The use of immunological therapies and stem cells differentiated in insulin-like secreting beta cells is at the forefront of therapies aimed at preserving beta cell function and the potential of a cure for type one diabetes. A recent study evaluated multiple cell lines with the NKp46 receptor present to examine the effects of a new antibody drug called 02. The result was that the 02-saporin significantly decreased the NK tumor cell line from proliferating.
Usage: 02-saporin was introducted to a NK tumor cell line while comparing another well-known drug with saporin attached.
Huang C, Gudlur S, Maricar S, Chen Z, Shebanova A, Sun Y, Saliba V, Xu C, Zou Y, Zhang J, Boujday S, Miserez A (2025) Peptide coacervates as intracellular delivery vehicles for synergistic cancer photothermal- and chemo-therapies. APL Bioeng 9(3):036101. doi: 10.1063/5.0279643 PMID: 40642324
Objective: To present a solution for intracellular delivery of large molecules using GW26 coacervate microdroplets (CMs), a peptide-based system, as a dual-function platform that not only facilitates the controlled release of therapeutic cargos but also enhances cancer cell death through photothermal therapy (PTT).
Summary: GW26 CMs exhibit high recruiting efficiency of photothermal (PT) materials—chlorin e6 (Ce6) and gold nanorods—with over 80% efficiency. These CMs demonstrate high cellular uptake in tumor cells, with 98% of CT26 colon carcinoma cells successfully internalizing Ce6-loaded CMs. The co-recruitment of the cytotoxic protein saporin enables synergistic PT and chemotherapeutic cancer treatments among all these cells, further enhancing the therapeutic effect, in some cases exhibiting a near-complete loss in cell viability. This approach combines efficient recruitment, controlled cargo release, and enhanced therapeutic efficacy, positioning GW26 CMs as a promising platform for multimodal cancer therapies.
Usage: Characterization of co-delivery of PT materials and saporin (4.5 ul) and their cell cytotoxicity in vitro.
