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

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…

• NS
  National Science Foundation

  Award: T32GM008620
• HH
  Howard Hughes Medical Institute
• BA
  Bill and Melinda Gates Foundation
• RT
  Research to Prevent Blindness
• NI
  National Institutes of Health

  Awards: R35GM118062, UG3AI150551, F30EY033642, U01AI142756, P30 EY034070, RM1HG009490, EY034070, T32GM008620
• NH
  National Human Genome Research Institute

  Award: RM1HG009490
• NE
  National Eye Institute

  Awards: R01EY009339, EY034070, P30 EY034070
• NI
  National Institute of General Medical Sciences

  Award: R35GM118062
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: U01AI142756, UG3AI150551
• SO
  School of Medicine, University of California, Irvine