Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo
Open accessAbstract
Efficient and safe delivery of the CRISPR/Cas system is one of the key challenges for genome-editing applications in humans. Herein, we designed and synthesized a series of biodegradable lipidlike compounds containing ester groups for the delivery of mRNA-encoding Cas9. Two lead materials, termed N-methyl-1,3-propanediamine (MPA)-A and MPA-Ab, showed a tunable rate of biodegradation. MPA-A with linear ester chains was degraded dramatically faster than MPA-Ab with branched ester chains in the presence of esterase or in wild-type mice. Most importantly, MPA-A and MPA-Ab demonstrated efficient delivery of Cas9 mRNA both in vitro and in vivo. Consequently, these biodegradable lipidlike nanomaterials merit further development as genome-editing delivery tools for biological and therapeutic applications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Biodegradable lipids can be applied to improve the biocompatibility of lipid nanoparticles.
“To improve the biocompatibility of lipid nanoparticles, biodegradable lipids can be applied76–78,108,179.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [179]
Biodegradable lipid derived materials designed by Zhang et al. achieved efficient delivery of Cas9 mRNA in vivo without significant organic damage.
“Biodegradable lipid derived materials designed by Zhang et al. achieved efficient delivery of Cas9 mRNA in vivo without significant organic damage.[232]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [232]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339 · see citing works
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210 · see citing works
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741 · see citing works
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 · see citing works
Knocking down barriers: advances in siRNA delivery
Whitehead, K. A., Langer, R., & Anderson, D. G. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2742 · Cited by 3,115 · see citing works
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 · see citing works
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
Platt, R. J., Chen, S., Zhou, Y., Yim, M. J., Swiech, L., Kempton, H. R., Dahlman, J. E., Parnas, O., Eisenhaure, T. M., Jovanovic, M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.014 · Cited by 2,001 · see citing works
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800 · see citing works
Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies
Mitragotri, S., Burke, P. A., & Langer, R. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4363 · Cited by 1,702 · see citing works
Lü, Y., Aimetti, A. A., Langer, R., & Gu, Z. (2016) · Nature Reviews Materials · doi:10.1038/natrevmats.2016.75 · Cited by 1,432 · see citing works
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · see citing works
Yin, H., Song, C.-Q., Dorkin, J. R., Zhu, L. J., Li, Y., Wu, Q., Park, A., Yang, J., Suresh, S., Bizhanova, A., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3471 · Cited by 876 · see citing works
Self-citationGenome editing with RNA-guided Cas9 nuclease in Zebrafish embryos
Chang, N., Sun, C., Gao, L., Zhu, D., Xu, X., Zhu, X., Xiong, J., & Xi, J. (2013) · Cell Research · doi:10.1038/cr.2013.45 · Cited by 819 · see citing works
Kauffman, K. J., Dorkin, J. R., Yang, J. H., Heartlein, M. W., DeRosa, F., Mir, F. F., Fenton, O. S., & Anderson, D. G. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b02497 · Cited by 785 · see citing works
Self‐assembled DNA nanoclews for the efficient delivery of CRISPR–Cas9 for genome editing
Sun, W., Ji, W., Hall, J. M., Hu, Q., Wang, C., Beisel, C. L., & Gu, Z. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201506030 · Cited by 629 · see citing works
Maier, M. A., Jayaraman, M., Matsuda, S., Liu, J., Barros, S., Querbes, W., Tam, Y. K., Ansell, S. M., Kumar, V., Qin, J., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.124 · Cited by 625 · see citing works
Self-citationDegradable lipid nanoparticles with predictable in vivo siRNA delivery activity
Whitehead, K. A., Dorkin, J. R., Vegas, A. J., Chang, P. H., Veiseh, O., Matthews, J., Fenton, O. S., Zhang, Y., Olejnik, K. T., Yesilyurt, V., et al. (2014) · Nature Communications · doi:10.1038/ncomms5277 · Cited by 615 · see citing works
Miller, J. B., Zhang, S., Kos, P., Xiong, H., Zhou, K., Perelman, S. S., Zhu, H., & Siegwart, D. J. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201610209 · Cited by 540 · see citing works
Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates
Dong, Y., Love, K. T., Dorkin, J. R., Sirirungruang, S., Zhang, Y., Chen, D., Bogorad, R. L., Yin, H., Chen, Y., Vegas, A. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322937111 · Cited by 488 · see citing works
Self-citationChen, D. L., Love, K. T., Chen, Y., Eltoukhy, A. A., Kastrup, C. J., Sahay, G., Jeon, A., Dong, Y., Whitehead, K. A., & Anderson, D. G. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301621z · Cited by 422 · see citing works
Self-citationKarikó, K., Muramatsu, H., Keller, J. M., & Weissman, D. (2012) · Molecular Therapy · doi:10.1038/mt.2012.7 · Cited by 282 · see citing works
Friedland, A. E., Baral, R., Singhal, P., Loveluck, K., Shen, S., Sanchez, M. E., Marco, E., Gotta, G. M., Maeder, M. L., Kennedy, E. M., et al. (2015) · Genome biology · doi:10.1186/s13059-015-0817-8 · Cited by 280 · see citing works
An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo
Li, B., Luo, X., Deng, B., Wang, J., McComb, D. W., Shi, Y., Gaensler, K. M. L., Tan, X., Dunn, A. L., Kerlin, B. A., et al. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b03528 · Cited by 261 · see citing works
Self-citationBioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery
Fenton, O. S., Kauffman, K. J., McClellan, R. L., Appel, E. A., Dorkin, J. R., Tibbitt, M. W., Heartlein, M. W., DeRosa, F., Langer, R., & Anderson, D. G. (2016) · Advanced Materials · doi:10.1002/adma.201505822 · Cited by 254 · see citing works
Recent Advances in Liposome Surface Modification for Oral Drug Delivery
Nguyen, T. X., Huang, L., Gauthier, M., et al. (2016) · Nanomedicine · doi:10.2217/nnm.16.9 · Cited by 235 · see citing works
Non-genetic engineering of cells for drug delivery and cell-based therapy
Wang, Q., Cheng, H., Peng, H., Zhou, H., Li, P. Y., & Langer, R. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.12.003 · Cited by 225 · see citing works
Safety profile of RNAi nanomedicines
Barros, S. A., & Gollob, J. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.06.007 · Cited by 126 · see citing works
Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo
Dong, Y., Dorkin, J. R., Wang, W., Chang, P., Webber, M. J., Tang, B. C., Yang, J., Ionita, I. A., Danino, D., DeRosa, F., et al. (2016) · Nano Letters · doi:10.1021/acs.nanolett.5b02428 · Cited by 111 · see citing works
Self-citationDu, D., Chang, N., Sun, S., Li, M., Yu, H., Liu, M., Liu, X., Wang, G., Li, H., Liu, X., et al. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.006 · Cited by 106 · see citing works
Direct observation of liquid crystals using cryo‐TEM: Specimen preparation and low‐dose imaging
Gao, M., Kim, Y., Zhang, C., Borshch, V. V., Zhou, S., Park, H., Jákli, A. I., Lavrentovich, O. D., Tamba, M. G., Kohlmeier, A., et al. (2014) · Microscopy Research and Technique · doi:10.1002/jemt.22397 · Cited by 104 · see citing works
Self-citationLipid‐Like Nanomaterials for Simultaneous Gene Expression and Silencing In Vivo
Dong, Y., Eltoukhy, A. A., Alabi, C. A., Khan, O. F., Omid Veiseh, A., Dorkin, J. R., Sirirungruang, S., Yin, H., Tang, B. C., Pelet, J. M., et al. (2014) · Advanced Healthcare Materials · doi:10.1002/adhm.201400054 · Cited by 60 · see citing works
Self-citationTamoxifen embedded in lipid bilayer improves the oncotarget of liposomal daunorubicin in vivo
Li, M. H., Yu, H., Wang, T. F., et al. (2014) · Journal of Materials Chemistry B · doi:10.1039/c3tb21423k · Cited by 55 · see citing works
Oda, H., Yamashita, H., Kosahara, K., et al. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42108-x · Cited by 52 · see citing works
Woodcock, S. R., Marwitz, A. J. V., Bruno, P., & Branchaud, B. P. (2006) · Organic Letters · doi:10.1021/ol0613463 · Cited by 51 · see citing works
Synthesis of a Series of Hydroxycarboxylic Acids as Standards for Oxidation of Nonanoic Acid
Rajabi, M., Lanfranchi, M., Campo, F., et al. (2013) · Synthetic Communications · doi:10.1080/00397911.2013.853800 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Self-citationThe challenge and prospect of mRNA therapeutics landscape
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., Xiao, H., Liang, X.-J., & Huang, Y. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107534 · Cited by 417 · see citing works
Evers, M. J. W., Kulkarni, J. A., van der Meel, R., Cullis, P. R., Vader, P., & Schiffelers, R. M. (2018) · Small Methods · doi:10.1002/smtd.201700375 · Cited by 332 · see citing works
How mRNA therapeutics are entering the monoclonal antibody field
Van Hoecke, L., & Roose, K. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-1804-8 · Cited by 205 · see citing works
Loughrey, D., & Dahlman, J. E. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00601 · Cited by 173 · see citing works
Nanoscale platforms for messenger RNA delivery
Li, B., Zhang, X., & Dong, Y. (2019) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1530 · Cited by 170 · see citing works
Nanoplatforms for mRNA Therapeutics
Meng, C., Chen, Z., Li, G., Welte, T., & Shen, H. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000099 · Cited by 130 · see citing works
RNA delivery biomaterials for the treatment of genetic and rare diseases
Zhao, W., Hou, X., Vick, O. G., & Dong, Y. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119291 · Cited by 82 · see citing works
Self-citationTanaka, H., Nakatani, T., Furihata, T., Tange, K., Nakai, Y., Yoshioka, H., Harashima, H., & Akita, H. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b01084 · Cited by 82 · see citing works
Blakney, A. K., McKay, P. F., Ibarzo Yus, B., Hunter, J. E., Dex, E. A., & Shattock, R. J. (2019) · ACS Nano · doi:10.1021/acsnano.9b01774 · Cited by 73 · see citing works
Zhang, C., Zhang, X., Zhao, W., Zeng, C., Li, W., Li, B., Luo, X., Li, J., Jiang, J., Deng, B., et al. (2019) · Nano Research · doi:10.1007/s12274-019-2308-9 · Cited by 61 · see citing works
Self-citation
- Authors
- Zhang, X., Li, B., Luo, X., Zhao, W., Jiang, J., Zhang, C., Gao, M., Chen, X., & Dong, Y.
- Affiliations
- Kent State University (US)
- Corresponding author
- Dong, Yizhou
- ORCID
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-07-19
- Volume
- 9
- Issue
- 30
- Pages
- 25481-25487
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- PMC
- PMC5896755
- OpenAlex
- W2726870238
- Cited by
- 107
- References
- 36
- Citations by year
- 2026: 3 · 2025: 17 · 2024: 11 · 2023: 12 · 2022: 17 · 2021: 9 · 2020: 15 · 2019: 12 · 2018: 10 · 2012: 1
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Association of Pharmaceutical Scientists
- National PKU Alliance
- Bayer HealthCare
- National Institute of General Medical Sciences (1R35GM119679)
- College of Pharmacy, Ohio State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- CRISPR/Cas genome editing, biodegradation, in vivo gene delivery, in vitro gene delivery
- MeSH terms
- Gene Editing, Animals, Esters, RNA, Messenger, Nanostructures, Mice, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
