CRISPR/Cas9-Based Genome Editing for Disease Modeling and Therapy: Challenges and Opportunities for Nonviral Delivery

Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety o...

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Veröffentlicht in:Chemical reviews Jg. 117; H. 15; S. 9874
Hauptverfasser: Wang, Hong-Xia, Li, Mingqiang, Lee, Ciaran M, Chakraborty, Syandan, Kim, Hae-Won, Bao, Gang, Leong, Kam W
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 09.08.2017
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ISSN:1520-6890, 1520-6890
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Abstract Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.
AbstractList Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.
Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.
Author Chakraborty, Syandan
Kim, Hae-Won
Wang, Hong-Xia
Bao, Gang
Li, Mingqiang
Leong, Kam W
Lee, Ciaran M
Author_xml – sequence: 1
  givenname: Hong-Xia
  surname: Wang
  fullname: Wang, Hong-Xia
  organization: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States
– sequence: 2
  givenname: Mingqiang
  orcidid: 0000-0002-5178-4138
  surname: Li
  fullname: Li, Mingqiang
  organization: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States
– sequence: 3
  givenname: Ciaran M
  surname: Lee
  fullname: Lee, Ciaran M
  organization: Department of Bioengineering, Rice University , Houston, Texas 77005, United States
– sequence: 4
  givenname: Syandan
  surname: Chakraborty
  fullname: Chakraborty, Syandan
  organization: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States
– sequence: 5
  givenname: Hae-Won
  orcidid: 0000-0001-6400-6100
  surname: Kim
  fullname: Kim, Hae-Won
  organization: Institute of Tissue Regeneration Engineering (ITREN) and Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 31116, Korea
– sequence: 6
  givenname: Gang
  orcidid: 0000-0001-5501-554X
  surname: Bao
  fullname: Bao, Gang
  organization: Department of Bioengineering, Rice University , Houston, Texas 77005, United States
– sequence: 7
  givenname: Kam W
  orcidid: 0000-0002-3269-5770
  surname: Leong
  fullname: Leong, Kam W
  organization: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28640612$$D View this record in MEDLINE/PubMed
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Snippet Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced...
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SubjectTerms CRISPR-Cas Systems - genetics
Gene Editing
Gene Transfer Techniques
Genetic Therapy - methods
Humans
Models, Biological
Title CRISPR/Cas9-Based Genome Editing for Disease Modeling and Therapy: Challenges and Opportunities for Nonviral Delivery
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