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The intersection of electromagnetic radiation and neuronal communication, focusing on the potential role of biophoton emission in brain function and neurodegenerative diseases is an emerging research area. Traditionally, it is believed that neurons encode and communicate information via electrochemical impulses, generating electromagnetic fields detectable by EEG and MEG. Recent discoveries indicate that neurons may also emit biophotons, suggesting an additional communication channel alongside the regular synaptic interactions. This dual signaling system is analyzed for its potential in synchronizing neuronal activity and improving information transfer, with implications for brain-like computing systems. The clinical relevance is explored through the lens of neurodegenerative diseases and intrinsically disordered proteins, where oxidative stress may alter biophoton emission, offering clues for pathological conditions, such as Alzheimer's and Parkinson's diseases. The potential therapeutic use of Low-Level Laser Therapy (LLLT) is also examined for its ability to modulate biophoton activity and mitigate oxidative stress, presenting new opportunities for treatment. Here, we invite further exploration into the intricate roles the electromagnetic phenomena play in brain function, potentially leading to breakthroughs in computational neuroscience and medical therapies for neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare no interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Adoptive transfer of antigen-specific regulatory T cells (Tregs) is a promising strategy to combat immunopathologies in transplantation and autoimmune diseases. However, their low frequency in peripheral blood poses challenges for both manufacturing and clinical application. Chimeric antigen receptors have been used to redirect the specificity of Tregs, using retroviral vectors. However, retroviral gene transfer is costly, time consuming, and raises safety issues. Here, we explored non-viral CRISPR-Cas12a gene editing to redirect Tregs, using human leukocyte antigen (HLA)-A2-specific constructs for proof-of-concept studies in transplantation models. Knock-in of an antigen-binding domain into the N terminus of CD3 epsilon (CD3ε) gene generates Tregs expressing a chimeric CD3ε-T cell receptor fusion construct (TRuC) protein that integrates into the endogenous TCR/CD3 complex. These CD3ε-TRuC Tregs exhibit potent antigen-dependent activation while maintaining responsiveness to TCR/CD3 stimulation. This enables preferential enrichment of TRuC-redirected Tregs over CD3ε knockout Tregs via repetitive CD3/CD28 stimulation in a good manufacturing practice-compatible expansion system. CD3ε-TRuC Tregs retained their phenotypic, epigenetic, and functional identity. In a humanized mouse model, HLA-A2-specific CD3ε-TRuC Tregs demonstrate superior protection of allogeneic HLA-A2 + skin grafts from rejection compared with polyclonal Tregs. This approach provides a pathway for developing clinical-grade CD3ε-TRuC-based Treg cell products for transplantation immunotherapy and other immunopathologies., Competing Interests: Declaration of interests W.D, J.K., H.-D.V., P.R., M.S.-H., and D.L.W. are listed as inventors on a patent application (EP4353252A1) related to the work presented in this manuscript. H.-D.V. is co-founder and CSO at CheckImmune GmbH. P.R., H.-D.V., O.W., and D.L.W. are co-founders of the startup TCBalance Biopharmaceuticals GmbH focused on Treg therapy. The Wagner lab at Charité received reagents related to gene editing in T cells from GenScript Inc. and Integrated DNA Technologies., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)