Nature chemical biology

Engineered IscB-ωRNA system with a wider range of targets for base editing

Updated

Abstract

Ten of 19 uncharacterized IscB proteins from uncultured microbes showed activity in mammalian cells.

  • The narrow targeting scope of IscB systems necessitates the identification of additional IscBs that recognize different target-adjacent motifs ().
  • IscB ortholog IscB.m16 was enhanced through protein and ωRNA engineering, expanding its TAM scope from MRNRAA to NNNGNA.
  • A variant named IscB.m16* was created, demonstrating improved targeting capabilities.
  • IscB.m16*-derived base editors showed robust base-editing efficiency in mammalian cells.
  • These base editors effectively restored Duchenne muscular dystrophy proteins in diseased mice using single adeno-associated virus delivery.

Simplified

Key numbers

46.15% ± 4.08%
Base-editing Efficiency Increase
Base-editing efficiency in HEK293T cells for *-.
NNNGNA
Expanded Range
range achieved by * compared to the previous MRNRAA.
3
Restoration of Expression
expression restoration in DMD mice after treatment.

Full Text

We can’t show the full text here under this license.

what lands in your inbox each week:

  • 📚7 fresh studies
  • 📝plain-language summaries
  • direct links to original studies
  • 🏅top journal indicators
  • 📅weekly delivery
  • 🧘‍♂️always free