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Delivery of CRISPR-Cas tools for in vivo genome editing therapy: Trends and challenges
Open accessAbstract
The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) genome editing technology opened the door to provide a versatile approach for treating multiple diseases. Promising results have been shown in numerous pre-clinical studies and clinical trials. However, a safe and effective method to deliver genome-editing components is still a key challenge for in vivo genome editing therapy. Adeno-associated virus (AAV) is one of the most commonly used vector systems to date, but immunogenicity against capsid, liver toxicity at high dose, and potential genotoxicity caused by off-target mutagenesis and genomic integration remain unsolved. Recently developed transient delivery systems, such as virus-like particle (VLP) and lipid nanoparticle (LNP), may solve some of the issues. This review summarizes existing in vivo delivery systems and possible solutions to overcome their limitations. Also, we highlight the ongoing clinical trials for in vivo genome editing therapy and recently developed genome editing tools for their potential applications.
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“The activity and fidelity of gene editing is heavily affected by the expression level and duration of the editors in the cells.”
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“Therefore, methods to deliver Cas9/sgRNA into the target cells profoundly influence its off-target effect”
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Metadata
- Authors
- Taha, E. A., Lee, J., & Hotta, A.
- Affiliations
- Ain Shams University (EG)
- Kyoto University (JP)
- Corresponding author
- Hotta, Akitsu
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 342
- Pages
- 345-361
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4205237319
- Cited by
- 259
- References
- 180
- Citations by year
- 2026: 48 · 2025: 72 · 2024: 70 · 2023: 51 · 2022: 18
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Greater South Information System
- Funders
- Takeda Pharmaceutical Co Ltd
- Japan Agency for Medical Research and Development (JP21bm0804005, JP21im0210115, JP19ek0109293, JP21bm0104001)
- Japan Science and Technology Agency (19H02924)
- National Center of Neurology and Psychiatry (28-6)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- CRISPR-Cas, in vivo gene editing, gene delivery, adeno-associated virus vectors, virus-like particles, lipid nanoparticles, immunogenicity, hepatotoxicity, off-target mutagenesis, chromosomal integration, clinical trials, genome editing tools
- MeSH terms
- Gene Editing, Liposomes, Nanoparticles, CRISPR-Cas Systems
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