CRISPR cascade: edited fungal polysaccharides for idiopathic pulmonary fibrosis with emphysema mimics - Letter to the Editor

Sep 29, 2026

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Letter to the Editor argues that CRISPR-Cas-based control of fungal polysaccharide production offers new possibilities for antifibrotic treatment, focusing on idiopathic pulmonary fibrosis (IPF) models with emphysema-like remodeling. It proposes that CRISPR cascade complexes can reprogram immunologic and structural interfaces driving fibrosis, targeting β-glucans, mannans, and chitin. The authors discuss potential mechanisms via macrophage polarization, fibroblast activation, TGF-β/IL-13/IL-10 cytokine circuits, and ECM remodeling, while outlining translational opportunities and current limitations including biosafety, ethical concerns, and validation needs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

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Letter to the Editor

Mechanistic rationale and translational potential

Potential applications in IPF and emphysema overlap

Biosafety, ethical, and ecological considerations

Conclusion

Ethical approval

Consent

Sources of funding

Author contributions

Conflicts of interest disclosure

Letter to the Editor CRISPR cascade: edited fungal polysforidiopathicpulmonary fibrosis with emphysema mimics Iman Osman Abufatima, MBBSa,*, Umair Ali, Pharm Db To the Editor, Renewed interest in CRISPR-Cas-based control of fungalpolysaccharide production holds new horizons in antifibrotictreatment with a specialty interest in idiopathic pulmonaryfibrosis (IPF) models featuring emphysema-like remodeling[1] .The paradigm of CRISPR Cascade complexes as precise editorsof fungal genomes offers a unique opportunity to reprogram theimmunologic and structural interfaces that underpin pulmonaryfibrosis[2] . This letter aims to highlight the emerging mechanisticrationale, translational potential, and current limitations ofCRISPR-edited fungal polysaccharides as novel modulators infibrotic-emphysematous disease. Fungal polysaccharides such as β-glucans, mannans, and chitinare increasingly recognized as bioactive molecules that orchestrateimmune-fibroblast cross-talk[3] . Such polymers can potentially reg -ulate alveolar macrophage polarization, fibroblast activation, andextracellular matrix (ECM) remodeling via cytokine circuitsinvol -ving TGF-β, IL-13, and IL-10[4] . By leveraging CRISPR-Cas sys -tems, whether Cas3-mediated repression of multigene or Cascadecomplexes for transcriptional control, biosynthetic pathways canbe precisely engineered to suppress pro-fibrotic glycosylationmotifs, induce anti-inflammatory conformations, or make immu -nologically inert scaffolds[5] . This molecular engineering is outsideof conventional antifungal or immunosuppressive paradigms, act -ing as a model for immunomodulatory biomolecules. In IPF and emphysema, shared injury-repair processes underliediscordant ECM kinetics. Fibrosis is characterized by exuberantcollagen deposition, whereas emphysema is typified by matrixdestruction[6] . Edited fungal polysaccharides could theoreticallyredress this imbalance by lessening epithelial oxidative stress, inhi -biting macrophage-driven inflammation, and augmenting epithelialregeneration[2] . Preliminary studies of precision-edited microbialglycans in organoid and murine models of fibrosis suggest thatthey have the ability to modulate myofibroblast differentiation aFaculty of Medicine, University of Medical Sciences and Technology, Khartoum,Sudan and bDepartment of Pharmacy, University of Swabi, Khyber Pakhtunkhwa,Pakistan Sponsorships or competing interests that maybe relevant to content are disclosedatthe end of this article. *Corresponding author. Address: Faculty of Medicine, University of MedicalSciences and Technology, El Riyad Area, Square No. 13, Khartoum, Sudan.E-mail: imanadam123@icloud.com (I. O. Abufatima). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is anopen access article distributed under the Creative Commons Attribution License 4.0(CCBY), which permits unrestricted use, distribution, and reproduction in any med-ium, provided the original work is properly cited. Annals of Medicine & Surgery (2026) 88:1017–1018Received 12 October 2025; Accepted 6 November 2025Published online 14 November 2025http://dx.doi.org/10.1097/MS9.0000000000004362 and enhance resolution pathways, meriting study in combinedfibrotic-destructive models[7] . Translationally, CRISPR-edited fungal products can serve asadjunct antifibrotic therapies or as delivery platforms for pro-resol -ving mediatorsand stem-cell-derived vesicles[1] . Moreover, theplat -forms can also serve as in vitro models fordeconstructing immune -epithelial interactions under fibrotic stress. Bioengineering platformintegration can also facilitate inhalable nanocarriers from fungalbiopolymers for targeted lung delivery[4] . Nonetheless, this technol -ogy demands rigorous biosafety evaluation, especially for fungalgene edits that may alter virulence determinants or environmentalpersistence. Despite their promise, vigilance is warranted. Gene editing infungal systems renders ethical and ecological

FAQs

What is the main idea of the letter regarding CRISPR cascade?

It highlights that CRISPR-Cas-based editing of fungal polysaccharide production may enable precise immunologic and structural reprogramming relevant to antifibrotic therapy in IPF models with emphysema-like remodeling.

How might edited fungal polysaccharides influence disease processes?

The letter proposes effects on immune-fibroblast cross-talk, including regulation of macrophage polarization, fibroblast activation, and extracellular matrix remodeling through cytokine-related circuits such as TGF-β, IL-13, and IL-10.

What limitations and safety concerns are emphasized for translation?

It stresses the need for rigorous biosafety evaluation, careful consideration of ethical/ecological risks such as horizontal gene transfer and immunogenic unpredictability, and controlled in vivo/ex vivo validation before clinical use.

Sep 29, 2026

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