# Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo

Article · An M, Raguram A, Du SW, Banskota S, Davis JR, Newby GA, Chen PZ, Palczewski K, Liu DR

- Archive id: doi:10.1038/s41587-023-02078-y
- Published: 2024-01-08
- Venue: Nature biotechnology
- DOI: https://doi.org/10.1038/s41587-023-02078-y
- PMID: 38191664
- PMCID: PMC11228131
- Citations: 242
- Source URL: https://doi.org/10.1038/s41587-023-02078-y
- PDF: https://europepmc.org/articles/PMC11228131/pdf
- Provenance: europepmc

## Abstract

Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture. In two mouse models of genetic blindness, single injections of v3 PE-eVLPs resulted in therapeutically relevant levels of prime editing in the retina, protein expression restoration and partial visual function rescue. Optimized PE-eVLPs support transient in vivo delivery of prime editor ribonucleoproteins, enhancing the potential safety of prime editing by reducing off-target editing and obviating the possibility of oncogenic transgene integration.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [CRISPR & Gene-Editing Therapies](https://space-kitty.com/topics/gene-editing-therapies)

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