Gene editing strategies to treat lysosomal disorders: The example of mucopolysaccharidoses

Adv Drug Deliv Rev. 2022 Dec:191:114616. doi: 10.1016/j.addr.2022.114616. Epub 2022 Nov 7.

Abstract

Lysosomal storage disorders are a group of progressive multisystemic hereditary diseases with a combined incidence of 1:4,800. Here we review the clinical and molecular characteristics of these diseases, with a special focus on Mucopolysaccharidoses, caused primarily by the lysosomal storage of glycosaminoglycans. Different gene editing techniques can be used to ameliorate their symptoms, using both viral and nonviral delivery methods. Whereas these are still being tested in animal models, early results of phase I/II clinical trials of gene therapy show how this technology may impact the future treatment of these diseases. Hurdles related to specific hard-to-reach organs, such as the central nervous system, heart, joints, and the eye must be tackled. Finally, the regulatory framework necessary to advance into clinical practice is also discussed.

Keywords: CRISPR/Cas; Gene delivery methods; Gene editing; Mucopolysaccharidoses; TALEN; Zinc finger.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Replacement Therapy / methods
  • Gene Editing
  • Lysosomal Storage Diseases* / drug therapy
  • Lysosomal Storage Diseases* / therapy
  • Lysosomes
  • Mucopolysaccharidoses* / diagnosis
  • Mucopolysaccharidoses* / genetics
  • Mucopolysaccharidoses* / therapy