E2 - Other Nonviral Delivery (including lipid nanoparticles and exosomes)
220: Engineered Virus-Like Particles for Transient Delivery of Prime Editor Ribonucleoprotein Complexes In Vivo
Type: Oral Abstract Session
Presentation Details
Session Title: Exosomes, Virus like Particles, and LNPs
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.
Meirui An1,2,3, Aditya Raguram1,2,3, Samuel W. Du4,5, Samagya Banskota1,2,3, Jessie R. Davis1,2,3, Gregory A. Newby1,2,3, Paul Z. Chen1,2,3, Krzysztof Palczewski4,5,6,7, David R. Liu1,2,3
1Merkin Institute of Transformative Technologies in Healthcare, Broad Institute, Cambridge, MA,2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA,3Howard Hughes Medical Institute, Harvard University, Cambridge, MA,4Gavin Herbert Eye Institute, Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA,5Department of Physiology and Biophysics, University of California, Irvine, CA,6Department of Chemistry, University of California, Irvine, MA,7Department of Molecular Biology and Biochemistry, University of California, Irvine, CA"
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