Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads

Adv Drug Deliv Rev. 2024 Aug:211:115346. doi: 10.1016/j.addr.2024.115346. Epub 2024 Jun 6.

Abstract

Gene editing technologies have the potential to correct genetic disorders by modifying, inserting, or deleting specific DNA sequences or genes, paving the way for a new class of genetic therapies. While gene editing tools continue to be improved to increase their precision and efficiency, the limited efficacy of in vivo delivery remains a major hurdle for clinical use. An ideal delivery vehicle should be able to target a sufficient number of diseased cells in a transient time window to maximize on-target editing and mitigate off-target events and immunogenicity. Here, we review major advances in novel delivery platforms based on cell-derived vesicles - extracellular vesicles and virus-like particles - for transient delivery of gene editing payloads. We discuss major findings regarding packaging, in vivo biodistribution, therapeutic efficacy, and safety concerns of cell-derived vesicles delivery of gene editing cargos and their potential for clinical translation.

Keywords: Biovesicles; CRISPR-Cas9; Cre recombinase; Delivery vehicles; Extracellular vesicles; Virus-like particles.

Publication types

  • Review

MeSH terms

  • Animals
  • Extracellular Vesicles* / metabolism
  • Gene Editing* / methods
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Humans