The DOI matches its Crossref record; 177 of the 180 references it cites were found in a registry or an index.
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.”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Taha et al., 2022
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“Therefore, methods to deliver Cas9/sgRNA into the target cells profoundly influence its off-target effect”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Taha et al., 2022
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A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R. (2016) · Nature · doi:10.1038/nature17946 · Cited by 5,437
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Search-and-replace genome editing without double-strand breaks or donor DNA
Anzalone, A. V., Randolph, P. B., Davis, J. R., Sousa, A. A., Koblan, L. W., Levy, J. M., Chen, P. J., Wilson, C., Newby, G. A., Raguram, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1711-4 · Cited by 4,767
Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage
Gaudelli, N. M., Komor, A. C., Rees, H. A., Packer, M. S., Badran, A. H., Bryson, D. I., & Liu, D. R. (2017) · Nature · doi:10.1038/nature24644 · Cited by 4,184
CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696
LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1
Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P., Lim, A., Osborne, C. S., Pawliuk, R., Morillon, E., et al. (2003) · Science · doi:10.1126/science.1088547 · Cited by 3,587
High-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728
In vivo genome editing using Staphylococcus aureus Cas9
Ran, F. A., Cong, L., Yan, W. X., Scott, D. A., Gootenberg, J. S., Kriz, A. J., Zetsche, B., Shalem, O., Wu, X., Makarova, K. S., et al. (2015) · Nature · doi:10.1038/nature14299 · Cited by 2,687
Research works printed but not linked: 5
- Audentes press release
- Audentes press release
- Walsh, 2020, Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates, N. Engl. J. Med., 383, 2439, 10.1056/NEJMoa2027906 · DOI · Paper page
- Mulligan, 2020, Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults, Nature, 586, 589, 10.1038/s41586-020-2639-4 · DOI · Paper page
- Gillmore, 2021, CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis, N. Engl. J. Med., 385, 493, 10.1056/NEJMoa2107454 · DOI · Paper page
Cited by
Sorted by citations
CRISPR technology: A decade of genome editing is only the beginning
Wang, J. Y., & Doudna, J. A. (2023) · Science · doi:10.1126/science.add8643 · Cited by 1,105
Off-target effects in CRISPR/Cas9 gene editing
Guo, C., Ma, X., Gao, F., & Guo, Y. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1143157 · Cited by 704
“Therefore, methods to deliver Cas9/sgRNA into the target cells profoundly influence its off-target effect (Lohia et al., 2022; Taha et al., 2022).”
MethodTherapeutic in vivo delivery of gene editing agents
Raguram, A., Banskota, S., & Liu, D. R. (2022) · Cell · doi:10.1016/j.cell.2022.03.045 · Cited by 552
Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy
Zong, Y., Lin, Y., Wei, T., & Cheng, Q. (2023) · Advanced Materials · doi:10.1002/adma.202303261 · Cited by 506
An, M., Raguram, A., Du, S. W., Banskota, S., Davis, J. R., Newby, G. A., Chen, P., Palczewski, K., & Liu, D. R. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-02078-y · Cited by 275
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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