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  3. Designed Minibinders Rewire Receptor Signaling To Enable Functional Human Myogenic Reprogramming.
  1. Home
  3. Designed Minibinders Rewire Receptor Signaling To Enable Functional Human Myogenic Reprogramming.

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Designed Minibinders Rewire Receptor Signaling to Enable Functional Human Myogenic Reprogramming.

Riya Keshri1,2, Zachary Foreman2,3, Phillip Barrett2

  • 1Department of Biochemistry, University of Washington, Seattle, United States.

Biorxiv : the Preprint Server for Biology
|May 7, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

Scientists used AI to design synthetic proteins that reprogram human cells into muscle cells. This breakthrough offers a new way to regenerate muscle tissue and combat sarcopenia, a common age-related condition.

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Area of Science:

  • Biotechnology
  • Regenerative Medicine
  • Cell Biology

Background:

  • Sarcopenia, the loss of muscle mass, presents a significant health challenge.
  • Direct myogenic somatic cell reprogramming for muscle regeneration is limited by control over cell fate signaling.
  • Existing methods lack precise control over the signaling pathways that dictate cell differentiation.

Purpose of the Study:

  • To overcome limitations in controlling cell fate during myogenic reprogramming.
  • To develop AI-designed synthetic ligands for precise receptor modulation.
  • To enable functional muscle tissue regeneration through controlled cell transdifferentiation.

Main Methods:

  • Screening de novo minibinders to identify effective protein cocktails.
  • Utilizing AI-designed receptor modulators to control extracellular signaling.
  • Investigating the roles of FGFR1/2c, ALK1, TGFBR2, and gp130 signaling pathways.
  • Engineering functional muscle tissues from reprogrammed human cells.

    • Main Results:

    • A synthetic protein cocktail, C6-DPC, was identified to drive efficient human fibroblast-to-muscle transdifferentiation.
    • C6-DPC reprogrammed signaling by activating pro-myogenic and suppressing anti-myogenic pathways.
    • Inhibition of inflammatory signaling via gp130 further enhanced cell conversion.
    • Engineered tissues from reprogrammed cells demonstrated robust structural and metabolic maturation, generating significant contractile forces.

    Conclusions:

    • AI-designed programmable synthetic ligands can rewrite receptor-level signaling to direct cell fate.
    • This approach enables functional muscle tissue regeneration, offering a potential therapeutic strategy for sarcopenia and muscle disorders.
    • Precise control over cell signaling pathways is key to overcoming barriers in regenerative medicine.