Asset

  • No.

    134

  • Asset Title

    Multiplexed Gene Editing and Control with Enhanced Cas12a

  • Organization

    Stanford University

  • Product Type

    Gene therapy

  • Therapeutic Area

    Genetic disorders

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    Multiplexed modulation of endogenous genes is crucial for sophisticated gene therapy and cell engineering. CRISPR-Cas12a systems enable versatile multiple genomic loci targeting by processing numerous crRNAs from a single transcript, however, their low efficiency has hindered applications in vivo. 

    • Through structure-guided protein engineering, inventors develop a hyper-efficient LbCas12a variant, termed hyperCas12a, with its catalytically dead version hyperdCas12a showing significantly enhanced efficacy for gene activation, particularly at low crRNA conditions. 

    • Inventors demonstrate that hyperdCas12a has minimal off-target effects compared to the wildtype system and exhibits enhanced activity for gene editing and repression. 

    • Delivery of the hyperdCas12a-activator and a single crRNA array simultaneously activating endogenous Oct4, Sox2, and Klf4 genes in the retina of postnatal mice alters the differentiation of retinal progenitor cells. 

    • The hyperCas12a system offers a versatile in vivo tool for a broad range of gene modulation and gene therapy applications. 

  • Patent

    WO2022174108A1

  • Publication

    Multiplexed genome regulation in vivo with hyper-efficient Cas12a. Nat Cell Biol. (2022)

  • Attachment

TOP