中文 |

Research Progress

Scientists Propose New Delivery Platform for Gene Therapy and Personalized Medicine

Jul 10, 2018

A research team led by Prof. YU Xuefeng at the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences reported a two-dimensional (2D) black phosphorus nanosheets (BPs)-based platform. The platform can carry out efficient cytosolic delivery of Cas9-sgRNA ribonucleoprotein complexes, providing efficient genome editing and gene silencing in vitro and in vivo.

The CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR-associated protein 9) system was originally derived from the adaptive prokaryotic immune system. It has been widely applied as a prominent tool in many fields, including transcription regulation, genome editing, in situ DNA/RNA detection, etc.

Traditional approaches delivering DNA components encoding Cas9 protein and sgRNA are limited by possible insertional mutagenesis and over-dosing, causing increasing risks of genetic disorders and off-target effects, respectively.

To overcome these problems, direct delivery of Cas9-sgRNA ribonucleoprotein complexes followed by sustained releases is regarded as an attractive strategy both in basic research and therapeutic applications.

Due to superior biodegradability and biocompatibility, distinctive physical and chemical properties, the researchers proposed that BPs had great potentials in cytosolic delivery of bioactive macromolecules, such as Cas9-sgRNA ribonucleoprotein complexes.

They reported a biodegradable two-dimensional (2D) delivery platform based on loading black phosphorus nanosheets (BPs) with Cas9 protein engineered with three nuclear localization signals (NLSs) at C terminus (Cas9N3).

This simple and versatile cytosolic delivery approach may extend to other bioactive macromolecules for biomedical applications, and its superior biocompatibility and biodegradability may open new avenues in gene therapy and personalized medicine.

The study entitled "Enhanced Cytosolic Delivery and Releases of CRISPR/Cas9 by Black Phosphorus Nanosheets for Genome Editing" was published in Angewandte Chemie International Edition.

This research was supported by the National Natural Science Foundation of China, International Cooperation Project for Science and Research Plan of Shenzhen, Frontier Science Key Programs of Chinese Academy of Sciences, and the Leverhulme Trust.

 

Figure 1. Design of the Cas9N3-BPs delivery platform and its intracellular delivery pathways. (Image by YU Xuefeng) 

 

Figure 2. (a) Intracellular delivery of Cas9N3-BPs; (b) Intracellular degradation of BPs from Cas9N3-BPs in a selected cell. (Image by YU Xuefeng) 

 

Figure 3. In vitro and in vivo genome editing and gene silencing induced by Cas9N3-BPs. (Image by YU Xuefeng) 

Contact Us
  • 86-10-68597521 (day)

    86-10-68597289 (night)

  • 86-10-68511095 (day)

    86-10-68512458 (night)

  • cas_en@cas.cn

  • 52 Sanlihe Rd., Xicheng District,

    Beijing, China (100864)

Copyright © 2002 - Chinese Academy of Sciences