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Genetic engineering

Genome editing by self-deliverable ribonucleoproteins

Nature Reviews Bioengineering volume 2, page 287 (2024)Cite this article

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CRISPR–Cas exploits a guide RNA to direct the Cas protein to specific genomic sites, where it can create double-stranded DNA breaks for precise DNA modifications. However, delivering these molecules into specific target cells for genome editing in vivo remains challenging, particularly in the brain owing to the restrictive nature of the blood–brain barrier. Current delivery methods mainly include viral vectors, which are limited by immunogenicity, undesired mutagenesis and manufacturing difficulties. Alternatively, non-viral delivery strategies, such as nanoparticle encapsulation, often require complex optimization and manufacturing processes.

The researchers fused the two genome-editing enzymes Cas9 and Cas12a to nuclear localization signal peptides to enable self-delivery and genome editing in mouse-derived neural progenitor cells and in mouse models in vivo. “We screened cell-penetrating peptides and identified nine peptides that improve the delivery of Cas9, reaching 72% genome editing efficiency in neural progenitor cells,” explains Doudna. Mechanistic studies suggest that cell-penetrating peptides promote ribonucleoprotein delivery through endocytosis.

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References

Original article

  • Chen, K. et al. Engineering self-deliverable ribonucleoproteins for genome editing in the brain. Nat. Commun. 15, 1727 (2024)

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  1. Nature Reviews Bioengineering https://www.nature.com/natrevbioeng/

    Nesma El-Sayed Ibrahim

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  1. Nesma El-Sayed Ibrahim
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Correspondence to Nesma El-Sayed Ibrahim.

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El-Sayed Ibrahim, N. Genome editing by self-deliverable ribonucleoproteins. Nat Rev Bioeng 2, 287 (2024). https://doi.org/10.1038/s44222-024-00179-0

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  • DOI: https://doi.org/10.1038/s44222-024-00179-0

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