Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors.
Publication/Presentation Date
4-28-2026
Abstract
Limb loss remains a significant clinical challenge, but regenerative medicine approaches such as gene therapy offer a promising strategy to trigger endogenous regeneration programs. Optimal vector configurations and molecular targets for appendicular skeletal repair are not well defined. Here, we leveraged insights from species with a high endogenous capacity for appendage regeneration to design an enhancer-directed gene delivery platform that functions during mouse digit regeneration, a well-characterized model for partial limb regeneration in mammals. Single-cell RNA sequencing of zebrafish caudal fin regeneration, combined with expression data in regenerating salamander limbs and mouse digit tips, implicated the SP family of transcription factors as conserved, epidermally expressed mediators of appendage regrowth. Null mutants of
Volume
123
Issue
17
First Page
2532804123
Last Page
2532804123
ISSN
1091-6490
Published In/Presented At
Brown, D. A., Koll, K. K., Brush, E., Darner, G., Curtis, T., Jr, Dvergsten, T., Tran, M., Milligan, C., Wolfson, D. W., Gonzalez, T. J., Jeffs, S., Ehrhardt, A., Bitolas, R., Landau, M., Reitz, K., Salven, D. S., Slota-Burtt, L. A., Snee, I., Singer-Freeman, E., Bhatia, S., … Poss, K. D. (2026). Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors. Proceedings of the National Academy of Sciences of the United States of America, 123(17), e2532804123. https://doi.org/10.1073/pnas.2532804123
Disciplines
Medicine and Health Sciences
PubMedID
41980086
Department(s)
Medical Education
Document Type
Article