Challenges and progress related to gene editing in rare skin diseases
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Adv Drug Deliv Rev. 2024 Mar 23:115294. doi: 10.1016/j.addr.2024.115294. Epub ahead of print. PMID: 38527624.

Challenges and progress related to gene editing in rare skin diseases

Authors: Josefina Piñón-Hofbauer 1Christina Guttmann-Gruber 1Verena Wally 1Anshu Sharma 2Iris K Gratz 3Ulrich Koller 4

Affiliation:

  1. EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  2. EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria.
  3. EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria; Center for Tumor Biology and Immunology, University of Salzburg, 5020 Salzburg, Austria.
  4. EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria. Electronic address: u.koller@salk.at.

Abstract:

Genodermatoses represent a large group of inherited skin disorders encompassing clinically-heterogeneous conditions that manifest in the skin and other organs. Depending on disease variant, associated clinical manifestations and secondary complications can severely impact patients’ quality of life and currently available treatments are transient and not curative. Multiple emerging approaches using CRISPR-based technologies offer promising prospects for therapy. Here, we explore current advances and challenges related to gene editing in rare skin diseases, including different strategies tailored to mutation type and structural organization of the affected gene, considerations for in vivo and ex vivo applications, the critical issue of delivery into the skin, and immune aspects of therapy. Against the backdrop of a landmark FDA approval for the first re-dosable gene replacement therapy for a rare genetic skin disorder, gene editing approaches are inching closer to the clinics and the possibility a local permanent cure for patients affected by these disorders

Keywords: CRISPR/Cas9; Epidermolysis bullosa; Gene Editing; Gene therapy; Genodermatoses; Ichthyosis.

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