Genome Editing via LNP-Based Delivery of Efficient and Stable CRISPR-Cas Editors

Tech ID: 32925 / UC Case 2023-015-0

Patent Status

Patent Pending

Brief Description

The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets. The programmable nature of these systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation. There is a need in the art for additional CRISPR-Cas systems with improved cleavage and manipulation under a variety of conditions and ones that are particularly thermostable under those conditions.


UCB researchers created a set of efficient CRISPR-Cas9 proteins from a thermostable Cas9 from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) through directed evolution. The gene editing activity of the evolved mutant proteins was improved by up to four orders of magnitude compared to the wild-type GeoCas9. The researchers showed that the gene editors based on the evolved GeoCas9 can be effectively assembled into lipid nanoparticles (LNP) for the rapid delivery to different cell lines in vitro as well as different organs or tissues in vivo. The LNP-based delivery strategy could also be extended to other gene editors.


Suggested uses

  • Genome editing
  • Genetic engineering
  • Gene therapy
  • Research tools (e.g., high-throughput screening of gene functions in cell lines and in vivo)
  • Creation of transgenic animal models


  • Gene editing activity greatly improved over wild type GeoCas9
  • Functions under different conditions than current CRISPR-Cas9 proteins (e.g, thermostable and enzymatically active in a wide temperature range)
  • Has an extended lifetime in human plasma

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  • Doudna, Jennifer A.

Other Information


CRISPR, gene edit, genome, gene therapy

Categorized As

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