Journal of Nanobiotechnology (May 2024)

Short cell-penetration peptide conjugated bioreducible polymer enhances gene editing of CRISPR system

  • Xiaobo Wang,
  • Chengyuan Cai,
  • Weiqi Lv,
  • Kechen Chen,
  • Jiaxin Li,
  • Kaitong Liao,
  • Yanqun Zhang,
  • Hongxin Huang,
  • Ying Lin,
  • Zhili Rong,
  • Xiaopin Duan

DOI
https://doi.org/10.1186/s12951-024-02554-w
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 15

Abstract

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Abstract CRISPR-based gene therapy offers precise targeting and specific editing of disease-related gene sequences, potentially yielding long-lasting treatment effects. However, efficient delivery remains a significant challenge for its widespread application. In this study, we design a novel short peptide-conjugated bioreducible polymer named TSPscp as a safe and effective delivery vector for the CRISPR system. Our results show that TSPscp markedly boosts transcriptional activation and genome editing activities of multiple CRISPR systems as confirmed by decomposition-seq and Deep-seq, which is resulted from its capability in facilitating delivery of plasmid DNA by promoting cellular uptake and lysosomal escape. Additionally, TSPscp further enhances genome editing of CRISPR by delivery of minicircle DNA, a condensed form of regular plasmid DNA. More importantly, TSPscp significantly improves delivery and genome editing of CRISPR system in vivo. In summary, our study highlights TSPscp as a promising delivery tool for CRISPR applications in vivo. Graphical Abstract

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