1. Academic Validation
  2. Cre Fused with RVG Peptide Mediates Targeted Genome Editing in Mouse Brain Cells In Vivo

Cre Fused with RVG Peptide Mediates Targeted Genome Editing in Mouse Brain Cells In Vivo

  • Int J Mol Sci. 2016 Dec 14;17(12):2104. doi: 10.3390/ijms17122104.
Zhiyuan Zou 1 2 Zhaolin Sun 3 Pan Li 4 Tao Feng 5 Sen Wu 6
Affiliations

Affiliations

  • 1 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. zzythinker@126.com.
  • 2 College of Life Science, Liaoning University, Shenyang 110036, China. zzythinker@126.com.
  • 3 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. szl305@126.com.
  • 4 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. lipan19900504@163.com.
  • 5 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. taocau@163.com.
  • 6 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. swu@cau.edu.cn.
Abstract

Cell penetrating Peptides (CPPs) are short Peptides that can pass through cell membranes. CPPs can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. RVG peptide (RVG hereinafter) is a 29-amino-acid CPP derived from a rabies virus glycoprotein that can cross the blood-brain barrier (BBB) and enter brain cells. However, whether RVG can be used for genome editing in the brain has not been reported. In this work, we combined RVG with Cre recombinase for Bacterial expression. The purified RVG-Cre protein cut plasmids in vitro and traversed cell membranes in cultured Neuro2a cells. By tail vein-injecting RVG-Cre into Cre reporter mouse lines mTmG and Rosa26lacZ, we demonstrated that RVG-Cre could target brain cells and achieve targeted somatic genome editing in adult mice. This direct delivery of the gene-editing Enzyme protein into mouse brains with RVG is much safer than plasmid- or viral-based methods, holding promise for further applications in the treatment of various brain diseases.

Keywords

Cre; RVG peptide; blood brain barrier; genome editing.

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