WP1 – Novel strategies to increase precision and efficacy of gene and epigenetic editing

WP1 aims at developing an expanded toolbox of improved technologies instrumental to accomplish the ambitious therapeutic goals of WP7-WP9. CRISPR/Cas9 and orthologous DNA targeting systems will be further perfected to  develop genome and base editors, tailored nucleases, and novel epigenetic editing systems. Also, a new set of user designed recombinases will be developed and combined with programmable vectors developed in WP2 to address large edits.

Specific WP’s objectives:

  1. Develop shorter and more precise CRISPR/Cas systems
  2. Develop strategies to enhance the efficiency of genome editing
  3. Improve epigenome editing tools towards in vivo applications
  4. Develop platform for advanced generation of programmable site-specific recombinases

Tasks:

  • Task 1.1: Turning inactive CRISPR/Cas systems into effective and precise tools to edit the mammalian genome
  • Task 1.2: Development of novel high-fidelity Cas9 proteins or orthologs variants
  • Task 1.3: Identification of cellular factors that increase efficiency of targeted genome editing
  • Task 1.4: Optimization of targeted epigenetic editing towards in vivo application in the liver
  • Task 1.5: Optimization of targeted epigenetic editing towards in vivo application in striated muscle
  • Task 1.6: Speeding up designer-recombinase evolution by the generation of “ISOR”-libraries
  • Task 1.7: Nanopore sequencing of recombinase libraries
  • Task 1.8: Optimization and characterization of “ISOR”-recombinases

Timeline:

WP1 timeline

WP leader: Anna Cereseto (UNITN)

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