HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute
Year: 2018
Type: article
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.
Source: Advanced Science
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
Funders: Guangdong Innovative and Entrepreneurial Research Team Program, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: Integrated Microphysiological System of Cerebral Organoid and Blood Vessel for Disease Modeling and Neuropsychiatric Drug screening, Systemic Inflammation in Microphysiological Models of Muscle and Vascular Disease, BD Biosciences Influx, A synthetic biology approach to analyze evolution of programmed bacterial death, Modeling Marfan Syndrome with iSMC-based Tissue-engineered Blood Vessel, G6737226027, Overcoming Immunosenescence by Nanoparticle-Mediated Activation, NRSA Training Core
OpenAlex ID: W2804452569