In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved]
Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of th...
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doaj-691385ca02c6425daeb3779339606fc82020-11-25T02:48:21ZengF1000 Research LtdF1000Research2046-14022017-12-01610.12688/f1000research.11243.112130In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved]Cia-Hin Lau0Yousin Suh1Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, SAR, ChinaInstitute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, USAAdeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics.https://f1000research.com/articles/6-2153/v1Aging |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cia-Hin Lau Yousin Suh |
spellingShingle |
Cia-Hin Lau Yousin Suh In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved] F1000Research Aging |
author_facet |
Cia-Hin Lau Yousin Suh |
author_sort |
Cia-Hin Lau |
title |
In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved] |
title_short |
In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved] |
title_full |
In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved] |
title_fullStr |
In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved] |
title_full_unstemmed |
In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease [version 1; referees: 2 approved] |
title_sort |
in vivo genome editing in animals using aav-crispr system: applications to translational research of human disease [version 1; referees: 2 approved] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2017-12-01 |
description |
Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics. |
topic |
Aging |
url |
https://f1000research.com/articles/6-2153/v1 |
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