| Autor: |
An, Meirui, Raguram, Aditya, Du, Samuel W., Banskota, Samagya, Davis, Jessie R., Newby, Gregory A., Chen, Paul Z., Palczewski, Krzysztof, Liu, David R. |
| Zdroj: |
Nature Biotechnology; Oct2024, Vol. 42 Issue 10, p1526-1537, 12p |
| Abstrakt: |
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. Delivery of prime editors in vivo is improved using virus-like particles. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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