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Development of Base Editors for safer genome editing – safeEdit

APOBEC1Base Editorsgene therapygenome editingMutationsterapia genica


Base editors are a new class of genomic editing tools and derive from the fusion of a DNA-targeting domain (typically Cas9) with a deaminase that induces base-specific editing. To limit unwanted mutations from aspecific activity of the deaminase on both RNA and DNA, we have developed mutants of the APOBEC1 deaminase to generate new base editors for safer genome editing and gene therapy.

Technical features

The main issue with the use of Base Editors regards the introduction of random mutations, known as off-targets, in the cell genome and transcriptome. To address this problem, we have selected a series of mutants of APOBEC1, a deaminase that acts on both DNA and RNA and is used for C>T or G>A editing, through bacterial screenings starting from a pool generated by mutagenic PCR. These mutants retain the ability to mutate DNA, but are unable to edit RNA. We then fused these APOBEC1 mutants with Cas9 to create new Base Editors. Sequencing experiments have confirmed their specificity and their reduced off-target activity, both on DNA and RNA. These new Base Editors can be used for safer genome editing and gene therapy, with a reduced risk of unintended mutations. TRL=3

Possible Applications

  • Safe and controlled DNA editing;
  • Gene therapy for diseases characterized by DNA alterations: Cancer, Genetic diseases, Rare Diseases;
  • Genome Editing for biotechnology and agrifood applications.


  • Lack of off-target effects, neither on DNA nor on RNA;
  • Versatility of the system in the genome editing field.