2026-01-27 カナダ・ブリティッシュコロンビア大学(UBC)
<関連情報>
- https://news.ubc.ca/2026/01/first-gene-editing-treatment-for-skin-conditions/
- https://www.sciencedirect.com/science/article/abs/pii/S193459092600024X
脂質ナノ粒子を用いた非ウイルス性in situ遺伝子編集によるヒト皮膚モデルにおける先天性魚鱗癬の原因遺伝子の編集 Lipid nanoparticle-based non-viral in situ gene editing of congenital ichthyosis-causing mutations in human skin models
Dilem Ceren Apaydin, Gaurav Sadhnani, Tiffany Carlaw, Jan Renziehausen, Elena Lizunova, Viviane Filor, Anna Hiller, Sophia Brumhard, Vincent Halim, Ulrike Brüning, Johannes Bischof, Rafaela Horbach Marodin, Daniel Z. Kurek, Manuel Rhiel, Sandra Ammann, Tatjana I. Cornu, Toni Cathomen, Leif Erik Sander, Benedikt Obermayer, Fabian Coscia …Sarah Hedtrich
Cell Stem Cell Available online: 27 January 2026
DOI:https://doi.org/10.1016/j.stem.2026.01.001
Graphical abstract
Highlights
- Laser-assisted topical LNP delivery enables in situ base editing in diseased human skin models
- Editing restores wild-type TGM1 gene (∼12%) and enzyme activity (∼30%)
- Topical LNP application shows excellent safety and low immunogenicity in vitro and in vivo
Summary
Autosomal recessive congenital ichthyosis (ARCI) refers to a group of rare, highly debilitating skin disorders that significantly impair patients’ quality of life and lack any effective treatment options. Here, we report clinically relevant in situ correction of the most common ARCI-causing mutation, TGM1 c.877-2A>G, a splice-site aberration, in human disease models. Targeted skin barrier modulation followed by topical application of the cytosine base editor eTd packaged into lipid nanoparticles yielded functional restoration of ∼30% of wild-type transglutaminase 1 activity in skin tissue. Toxicity studies and comprehensive off-target analysis demonstrated an excellent safety profile even after repeated application, without systemic distribution of the lipid nanoparticles or the genetic cargo as determined via highly sensitive methods, including desorption electrospray ionization (DESI) metabolic imaging. This study presents comprehensive preclinical data on the feasibility of in situ gene correction of genodermatoses-causing mutations, showcasing its therapeutic potential and paving the way for curative next-generation treatments for severe genetic skin diseases.
