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One-Time Genome Editing Enables Long-Term Weight-Loss Drug Production in Mice

The method combines lipid nanoparticle delivery with homology-independent integration, sustaining therapeutic peptide release to reverse diet-induced obesity.

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Overview

  • Researchers at the University of Osaka used lipid nanoparticle-delivered homology-independent targeted integration to insert a secretion-enabled Exenatide gene into the albumin locus of mouse hepatocytes.
  • A single treatment produced elevated plasma Exenatide levels for more than 28 weeks.
  • Edited mice consumed 29% less food and lost 34% of their body weight compared to untreated controls.
  • Treated animals demonstrated improved glucose tolerance, reduced HbA1c and enhanced insulin sensitivity without detectable adverse effects.
  • Genomic analyses revealed minimal off-target editing and stable liver enzyme profiles, and authors propose the one-time intervention as an alternative to regular biologic dosing for complex metabolic diseases.