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HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051382/ https://www.ncbi.nlm.nih.gov/pubmed/30027026 http://dx.doi.org/10.1002/advs.201700540 |
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author | 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. |
author_facet | 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. |
author_sort | Lao, Yeh‐Hsing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6051382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60513822018-07-19 HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute 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. Adv Sci (Weinh) Full Papers 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. John Wiley and Sons Inc. 2018-05-18 /pmc/articles/PMC6051382/ /pubmed/30027026 http://dx.doi.org/10.1002/advs.201700540 Text en © 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers 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. HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute |
title | HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute |
title_full | HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute |
title_fullStr | HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute |
title_full_unstemmed | HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute |
title_short | HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute |
title_sort | hpv oncogene manipulation using nonvirally delivered crispr/cas9 or natronobacterium gregoryi argonaute |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051382/ https://www.ncbi.nlm.nih.gov/pubmed/30027026 http://dx.doi.org/10.1002/advs.201700540 |
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