HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute. Issue 7 (18th May 2018)

• Record Type: Journal Article
• Authors: Lao, Yeh‐Hsing; Li, Mingqiang; Gao, Madeleine A.; Shao, Dan; Chi, Chun‐Wei; Huang, Dantong; Chakraborty, Syandan; Ho, Tzu‐Chieh; Jiang, Weiqian; Wang, Hong‐Xia; Wang, Sihong; Leong, Kam W.
• Is Part Of: Advanced science. Volume 5:Issue 7(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-05-18
• Subjects: CRISPR/Cas9 -- gene delivery -- gene editing -- gene silencing -- human papillomavirus (HPV) -- Natronobacterium gregoryi Argonaute (NgAgo); Science -- Periodicals; 505
• DOI: 10.1002/advs.201700540
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: CRISPR/Cas9 technology enables targeted gene editing; yet, the efficiency and specificity remain unsatisfactory, particularly for the nonvirally delivered, plasmid‐based CRISPR/Cas9 system. To tackle this, a self‐assembled micelle is developed and evaluated for human papillomavirus (HPV) E7 oncogene disruption. The optimized micelle enables effective delivery of Cas9 plasmid with a transient transgene expression profile, benefiting the specificity of Cas9 recognition. Furthermore, the feasibility of using the micelle is explored for another nucleic acid‐guided nuclease system, Natronobacterium gregoryi Argonaute (NgAgo). Both systems are tested in vitro and in vivo to evaluate their therapeutic potential. Cas9‐mediated E7 knockout leads to significant inhibition of HPV‐induced cancerous activity both in vitro and in vivo, while NgAgo does not show significant E7 inhibition on the xenograft mouse model. Collectively, this micelle represents an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine‐based therapeutics. Abstract : A self‐assembled micelle is optimized to deliver CRISPR/Cas9 and Natronobacterium gregoryi Argonaute (NgAgo) systems for human papillomavirus (HPV) oncogene E7 manipulation. The Cas9 plasmid delivery can disrupt the oncogene in vitro and in vivo, leading to improved therapeutic outcome. However, the possibility of delivering NgAgo plasmid for HPV E7 knockdown remains unclear.