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Updated: Jan 24, 2026
08:12
A Web-Based Workflow for Selecting Gene- and Tissue-Specific Enhancers
Published on: July 18, 2025
636
Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors
Biorxiv : the Preprint Server for Biology
|January 23, 2026
Summary
Gene therapy using SP transcription factors and FGF8 can promote limb regeneration. This approach leverages conserved genetic pathways to enhance appendage regrowth after injury in mammals.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Developmental Biology
Background:
- Limb loss presents a significant clinical challenge.
- Regenerative medicine, particularly gene therapy, shows promise for triggering endogenous regeneration.
- Optimal gene targets and delivery methods for skeletal repair are not well defined.
Purpose of the Study:
- To identify conserved molecular targets for appendage regeneration.
- To develop an enhancer-directed gene delivery platform for limb regeneration.
- To investigate the role of SP transcription factors in mammalian limb regrowth.
Main Methods:
- Single-cell RNA sequencing of zebrafish fin regeneration.
- Analysis of regenerating salamander limbs and mouse digit tips.
- Conditional knockout of SP6/SP8 in mouse epidermis and AAV-mediated gene delivery of FGF8.
Main Results:
- SP6 and SP8 transcription factors are conserved epidermal mediators of appendage regrowth.
- Impaired digit regeneration in SP-deficient mice involves an IL-17 mediated osteoclastogenic program.
- Enhancer-directed FGF8 expression partially rescued regeneration in knockout mice and accelerated it in wildtype mice.
Conclusions:
- SP transcription factors are key regulators of mammalian limb regeneration.
- A gene therapy framework using tissue-specific enhancers can promote appendage regrowth.
- This approach offers potential for new limb healing interventions.
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