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Review
. 2023 Sep 26:34:102040.
doi: 10.1016/j.omtn.2023.102040. eCollection 2023 Dec 12.

CRISPR-Cas9 delivery strategies with engineered extracellular vesicles

Yaoyao Lu  1 , Kelly Godbout  1 , Gabriel Lamothe  1 , Jacques P Tremblay  1
Affiliations
Review

CRISPR-Cas9 delivery strategies with engineered extracellular vesicles

Yaoyao Lu et al. Mol Ther Nucleic Acids. .

Abstract

Therapeutic genome editing has the potential to cure diseases by directly correcting genetic mutations in tissues and cells. Recent progress in the CRISPR-Cas9 systems has led to breakthroughs in gene editing tools because of its high orthogonality, versatility, and efficiency. However, its safe and effective administration to target organs in patients is a major hurdle. Extracellular vesicles (EVs) are endogenous membranous particles secreted spontaneously by all cells. They are key actors in cell-to-cell communication, allowing the exchange of select molecules such as proteins, lipids, and RNAs to induce functional changes in the recipient cells. Recently, EVs have displayed their potential for trafficking the CRISPR-Cas9 system during or after their formation. In this review, we highlight recent developments in EV loading, surface functionalization, and strategies for increasing the efficiency of delivering CRISPR-Cas9 to tissues, organs, and cells for eventual use in gene therapies.

Keywords: CRISPR-Cas9; MT: Exploiting Extracellular Vesicles as Therapeutic Agents Special Issue; delivery; extracellular vesicles; gene therapy; tissue targeting.

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Conflict of interest statement

The authors declare that the manuscript was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict.

Figures

None
Graphical abstract
Figure 1
Figure 1
Methods for loading CRISPR-Cas9 components into EVs (Left) Post-isolation loading method. EVs are produced by unmodified parent cells. The components of the CRISPR-Cas9 system are loaded into EVs after their isolation and purification. (Right) Pre-isolation loading method. The components of the CRISPR-Cas9 system are transfected into parent cells. EVs are harvested and will contain the exogenous nucleic acid material by natural EV production route.
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