A radioactive CRISPR interference system using 89Zr-labeled LbCas12a

J Control Release. 2024 Jan:365:703-715. doi: 10.1016/j.jconrel.2023.11.045. Epub 2023 Dec 7.

Abstract

Recently, CRISPR proteins have been recognized as promising candidates for drug development. However, there is still a lack of substances with the appropriate sensitivity and stability for targeted drug delivery systems. 89Zr is a radioactive isotope that emits positrons, allowing real-time in vivo tracking with proven safety. In this study, we confirmed that labeling with 89Zr did not compromise the functionality of CRISPR proteins during in vivo behavioral imaging. Furthermore, we demonstrated the therapeutic efficacy of the CRISPR interference system in a mouse model of liver fibrosis, highlighting the theragnostic potential of isotope-labeled CRISPR proteins. The findings of this research could contribute to various aspects of ongoing clinical studies exploring the in vivo applications of CRISPR proteins.

Keywords: CRISPR interference; LbCas12a; Radiolabeled CRISPR; Radiolabeled therapy; Zirconium-89.

MeSH terms

  • Animals
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • Isotope Labeling
  • Mice
  • Positron-Emission Tomography* / methods
  • Radioisotopes
  • Tissue Distribution
  • Zirconium

Substances

  • Zirconium
  • Radioisotopes