Engineered Virus-like Particles for Efficient in Vivo Delivery of Therapeutic Proteins
Open accessAbstract
Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.
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In the liver of C67BL/6J mice, VLPs targeting Pcsk9 showed 63% editing.
“In the liver of C67BL/6J mice, they targeted Pcsk9, a therapeutically relevant gene involved in cholesterol homeostasis, and showed 63% editing.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [83]
This study provided compelling evidence for the use of VLPs for in vitro and in vivo applications.
“This study provided compelling evidence for the use of VLPs for in vitro and in vivo applications.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [83]
VLPs injected subretinally in rd12 mouse (LCA model with Rep65 mutation) resulted in 21% editing in RPE cells and rescue of visual function as measured by ERG five weeks postinjection.
“Five weeks postinjection, they reported 21% editing in the RPE cells and the rescue of visual function, as measured by ERG.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [83]
In primary human and mouse fibroblasts, VLP-mediated base editing could be achieved with more than 95% efficiency.
“They showed that in primary human and mouse fibroblasts, VLP-mediated base editing could be achieved with more than 95% efficiency.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [83]
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Pushko, P., Pumpens, P., & Grens, E. (2013) · Intervirology · doi:10.1159/000346773 · Cited by 5,970 · see citing works
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 · see citing works
Self-citationProgrammable 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 · see citing works
Self-citationSequence Variations in <i>PCSK9,</i> Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181 · see citing works
Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
Abifadel, M., Varret, M., Rabès, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., et al. (2003) · Nature Genetics · doi:10.1038/ng1161 · Cited by 2,985 · see citing works
Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors
Anzalone, A. V., Koblan, L. W., & Liu, D. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0561-9 · Cited by 2,237 · see citing works
Self-citationKosicki, M., Tomberg, K., & Bradley, A. (2018) · Nature Biotechnology · doi:10.1038/nbt.4192 · Cited by 1,883 · see citing works
Base editing: precision chemistry on the genome and transcriptome of living cells
Rees, H. A., & Liu, D. R. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0059-1 · Cited by 1,675 · see citing works
Self-citationCRISPResso2 provides accurate and rapid genome editing sequence analysis
Clement, K., Rees, H. A., Canver, M. C., Gehrke, J. M., Farouni, R., Hsu, J. Y., Cole, M. A., Liu, D. R., Joung, J. K., Bauer, D. E., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0032-3 · Cited by 1,632 · see citing works
Self-citationCRISPR-engineered T cells in patients with refractory cancer
Stadtmauer, E. A., Fraietta, J. A., Davis, M. M., Cohen, A. D., Weber, K. L., Lancaster, E., Mangan, P. A., Kulikovskaya, I., Gupta, M., Chen, F., et al. (2020) · Science · doi:10.1126/science.aba7365 · Cited by 1,478 · see citing works
Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy
Mercuri, E., Darras, B. T., Chiriboga, C. A., Day, J. W., Campbell, C., Connolly, A. M., Iannaccone, S. T., Kirschner, J., Kuntz, N. L., Saito, K., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1710504 · Cited by 1,433 · see citing works
Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., & Hobbs, H. H. (2005) · Nature Genetics · doi:10.1038/ng1509 · Cited by 1,381 · see citing works
Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems
Nishida, K., Arazoe, T., Yachie, N., Banno, S., Kakimoto, M., Tabata, M., Mochizuki, M., Miyabe, A., Araki, M., Hara, K. Y., et al. (2016) · Science · doi:10.1126/science.aaf8729 · Cited by 1,349 · see citing works
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126 · cited 1× · see citing works
“Recently developed gene editing agents enable the precise manipulation of genomic DNA in living organisms and raise the possibility of treating the root cause of many genetic diseases (Anzalone et al., 2020; Doudna, 2020; Newby and Liu, 2021).”
BackgroundCre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
Deverman, B. E., Pravdo, P. L., Simpson, B. P., Kumar, S. R., Chan, K. Y., Banerjee, A., Wu, W.-L., Yang, B., Huber, N., Pasca, S. P., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3440 · Cited by 1,061 · see citing works
Richter, M. F., Zhao, K. T., Eton, E., Lapinaite, A., Newby, G. A., Thuronyi, B. W., Wilson, C., Koblan, L. W., Zeng, J., Bauer, D. E., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0453-z · Cited by 1,020 · see citing works
Self-citationImproving cytidine and adenine base editors by expression optimization and ancestral reconstruction
Koblan, L. W., Doman, J. L., Wilson, C., Levy, J. M., Tay, T., Newby, G. A., Maianti, J. P., Raguram, A., & Liu, D. R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4172 · Cited by 944 · see citing works
Self-citationClinical use of lentiviral vectors
Milone, M. C., & O’Doherty, U. (2018) · Leukemia · doi:10.1038/s41375-018-0106-0 · Cited by 930 · see citing works
Enhanced prime editing systems by manipulating cellular determinants of editing outcomes
Chen, P. J., Hussmann, J. A., Yan, J., Knipping, F., Ravisankar, P., Chen, P.-F., Chen, C.-D., Nelson, J. W., Newby, G. A., Şahin, M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.018 · Cited by 820 · see citing works
Self-citationCIRCLE-Seq: A highly sensitive in vitro screen for genome-wide CRISPR-cas9 nuclease off-targets
Tsai, S. Q., Nguyen, N. T., Malagon-Lopez, J., Topkar, V. V., Aryee, M. J., & Joung, J. K. (2017) · Nature Methods · doi:10.1038/nmeth.4278 · Cited by 814 · see citing works
Leber congenital amaurosis: Genes, proteins and disease mechanisms
den Hollander, A. I., Roepman, R., Koenekoop, R. K., & Cremers, F. P. M. (2008) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2008.05.003 · Cited by 811 · see citing works
In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates
Musunuru, K., Chadwick, A. C., Mizoguchi, T., Garcia, S. P., DeNizio, J. E., Reiss, C. W., Wang, K., Iyer, S., Dutta, C., Clendaniel, V., et al. (2021) · Nature · doi:10.1038/s41586-021-03534-y · Cited by 793 · see citing works
Self-citationIn vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9
Swiech, L., Heidenreich, M., Banerjee, A., Habib, N., Li, Y., Trombetta, J., Sur, M., & Zhang, F. (2015) · Nature Biotechnology · doi:10.1038/nbt.3055 · Cited by 772 · cited 1× · see citing works
“We produced v4 BE-eVLPs that install a silent mutation in mouse Dnmt1, a genomic locus known to be amenable to nuclease-mediated indel formation and adenine base editing in vivo (Levy et al., 2020; Swiech et al., 2015).”
MethodThorne, R. G., & Nicholson, C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509425103 · Cited by 641 · see citing works
Wei, T., Cheng, Q., Min, Y.-L., Olson, E. N., & Siegwart, D. J. (2020) · Nature Communications · doi:10.1038/s41467-020-17029-3 · Cited by 603 · see citing works
Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing
Leibowitz, M. L., Papathanasiou, S., Doerfler, P. A., Blaine, L. J., Sun, L., Yao, Y., Zhang, C.-Z., Weiss, M. J., & Pellman, D. (2021) · Nature Genetics · doi:10.1038/s41588-021-00838-7 · Cited by 583 · see citing works
Fitzgerald, K. J., Frank-Kamenetsky, M. D., Shulga‐Morskaya, S., Liebow, A., Bettencourt, B. R., Sutherland, J. E., Hutabarat, R. M., Clausen, V. A., Karsten, V., Cehelsky, J. E., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61914-5 · Cited by 574 · see citing works
Altering the Tropism of Lentiviral Vectors through Pseudotyping
Cronin, J., Zhang, X.-Y., & Reiser, J. (2005) · Current Gene Therapy · doi:10.2174/1566523054546224 · Cited by 540 · see citing works
CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors
Wang, D., Zhang, F., & Gao, G. (2020) · Cell · doi:10.1016/j.cell.2020.03.023 · Cited by 526 · see citing works
Directed evolution of adenine base editors with increased activity and therapeutic application
Gaudelli, N. M., Lam, D. K., Rees, H. A., Solá-Esteves, N. M., Barrera, L. A., Born, D. A., Edwards, A., Gehrke, J. M., Lee, S., Liquori, A., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0491-6 · Cited by 518 · see citing works
In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice
Koblan, L. W., Erdos, M. R., Wilson, C., Cabral, W. A., Levy, J. M., Xiong, Z., Tavarez, U. L., Davison, L. M., Gete, Y. G., Mao, X., et al. (2021) · Nature · doi:10.1038/s41586-020-03086-7 · Cited by 479 · see citing works
Self-citationEvaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors
Doman, J. L., Raguram, A., Newby, G. A., & Liu, D. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0414-6 · Cited by 473 · see citing works
Self-citationLevy, J. M., Yeh, W.-H., Pendse, N. D., Davis, J. R., Hennessey, E., Butcher, R. M., Koblan, L. W., Comander, J., Liu, Q., & Liu, D. R. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0501-5 · Cited by 472 · see citing works
Self-citationRees, H. A., Komor, A. C., Yeh, W.-H., Caetano‐Lopes, J., Warman, M. L., Edge, A. S. B., & Liu, D. R. (2017) · Nature Communications · doi:10.1038/ncomms15790 · Cited by 422 · see citing works
Self-citationSmall molecule–triggered Cas9 protein with improved genome-editing specificity
Davis, K. M., Pattanayak, V., Thompson, D. B., Zuris, J. A., & Liu, D. R. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1793 · Cited by 418 · see citing works
Self-citationBase editing of haematopoietic stem cells rescues sickle cell disease in mice
Newby, G. A., Yen, J. S., Woodard, K. J., Mayuranathan, T., Lazzarotto, C. R., Li, Y., Sheppard, H., Porter, S. N., Yao, Y., Mayberry, K. D., et al. (2021) · Nature · doi:10.1038/s41586-021-03609-w · Cited by 390 · see citing works
Self-citationIn vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels
Rothgangl, T., Dennis, M. K., Lin, P. J. C., Oka, R., Witzigmann, D., Villiger, L., Qi, W., Hruzova, M., Kissling, L., Lenggenhager, D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00933-4 · Cited by 378 · see citing works
The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population
Hooper, A. J., Marais, A. D., Tanyanyiwa, D. M., & Burnett, J. R. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.08.039 · Cited by 363 · see citing works
Gee, P., Lung, M. S. Y., Okuzaki, Y., Sasakawa, N., Iguchi, T., Makita, Y., Hozumi, H., Miura, Y., Yang, L. F., Iwasaki, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14957-y · Cited by 363 · see citing works
Self-citationMangeot, P. E., Risson, V., Fusil, F., Marnef, A., Laurent, E., Blin, J., Mournetas, V., Massouridès, E., Sohier, T. J. M., Corbin, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-07845-z · Cited by 346 · see citing works
In vivo CRISPR editing with no detectable genome-wide off-target mutations
Akçakaya, P., Bobbin, M. L., Guo, J. A., Malagon-Lopez, J., Clement, K., Garcia, S. P., Fellows, M. D., Porritt, M. J., Firth, M. A., Carreras, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0500-9 · Cited by 316 · see citing works
SERREZE, D. V., Leiter, E. H., Christianson, G. J., et al. (1994) · Diabetes · doi:10.2337/diab.43.3.505 · Cited by 290 · see citing works
CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity
Lazzarotto, C. R., Malinin, N. L., Li, Y., Zhang, R., Yang, Y., Lee, G., Cowley, E., He, Y., Lan, X., Jividen, K., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0555-7 · Cited by 283 · see citing works
Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes
LeibundGut‐Landmann, S., Waldburger, J., Krawczyk, M., Otten, L., Suter, T. B., Fontana, A., Acha‐Orbea, H., & Reith, W. (2004) · European Journal of Immunology · doi:10.1002/eji.200424964 · Cited by 277 · see citing works
Circularly permuted and PAM-modified Cas9 variants broaden the targeting scope of base editors
Huang, T. P., Zhao, K. T., Miller, S. M., Gaudelli, N. M., Oakes, B. L., Fellmann, C., Savage, D. F., & Liu, D. R. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0134-y · Cited by 277 · see citing works
Self-citationTherapeutic base editing of human hematopoietic stem cells
Zeng, J., Wu, Y., Ren, C., Bonanno, J., Shen, A. H., Shea, D. N., Gehrke, J. M., Clement, K., Luk, K., Yao, Q., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0790-y · Cited by 277 · see citing works
Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy
Cideciyan, A. V. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2010.04.002 · Cited by 256 · see citing works
Taylor, A. W. (2009) · Eye · doi:10.1038/eye.2008.382 · Cited by 253 · see citing works
Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos
Alanis-Lobato, G., Zohren, J., McCarthy, A., Fogarty, N. M. E., Kubikova, N., Hardman, E., Greco, M., Wells, D., Turner, J. M. A., & Niakan, K. K. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004832117 · Cited by 234 · see citing works
Webber, B. R., Lonetree, C.-L., Kluesner, M. G., Johnson, M. J., Pomeroy, E. J., Diers, M. D., Lahr, W. S., Draper, G. M., Slipek, N. J., Smeester, B. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13007-6 · Cited by 232 · see citing works
Self-citationQuantitative evaluation of chromosomal rearrangements in gene-edited human stem cells by CAST-Seq
Turchiano, G., Andrieux, G., Klermund, J., Blattner, G., Pennucci, V., el Gaz, M., Monaco, G., Poddar, S., Mussolino, C., Cornu, T. I., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.02.002 · Cited by 231 · see citing works
In vivo base editing of post-mitotic sensory cells
Yeh, W.-H., Chiang, H., Rees, H. A., Edge, A. S. B., & Liu, D. R. (2018) · Nature Communications · doi:10.1038/s41467-018-04580-3 · Cited by 225 · see citing works
Self-citationProtein delivery using engineered virus-like particles
Kaczmarczyk, S. J., Sitaraman, K., Young, H. A., Hughes, S. H., & Chatterjee, D. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101874108 · Cited by 220 · see citing works
Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering
Hamilton, J. R., Tsuchida, C. A., Nguyen, D. N., Shy, B. R., McGarrigle, E. R., Espinoza, C. R. S., Carr, D., Blaeschke, F., Marson, A., & Doudna, J. A. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109207 · Cited by 208 · see citing works
Pang, J., Chang, B., Hawes, N. L., Hurd, R. E., Davisson, M. T., Li, J., Noorwez, S. M., Malhotra, R., McDowell, J. H., Kaushal, S., et al. (2005) · PubMed · Cited by 206 · see citing works
Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models
Chandler, R. J., Sands, M. S., & Venditti, C. P. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.009 · Cited by 203 · see citing works
Yao, X., Lyu, P., Yoo, K. W., Yadav, M., Singh, R. N., Atala, A., & Lu, B. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12076 · Cited by 197 · see citing works
Lentivirus pre-packed with Cas9 protein for safer gene editing
Choi, J., Dang, Y., Abraham, S., Ma, H., Zhang, J., Guo, H., Cai, Y., Mikkelsen, J. G., Wu, H., Shankar, P., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.27 · Cited by 192 · see citing works
In vivo somatic cell base editing and prime editing
Newby, G. A., & Liu, D. R. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.002 · Cited by 192 · see citing works
Self-citationYu, Y., Leete, T., Born, D. A., Young, L., Barrera, L. A., Lee, S., Rees, H. A., Ciaramella, G., & Gaudelli, N. M. (2020) · Nature Communications · doi:10.1038/s41467-020-15887-5 · Cited by 190 · see citing works
Yeh, W.-H., Shubina-Oleinik, O., Levy, J. M., Pan, B., Newby, G. A., Wornow, M., Burt, R., Chen, J. C., Holt, J. R., & Liu, D. R. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay9101 · Cited by 179 · see citing works
Self-citationViral Vectors: The Road to Reducing Genotoxicity
David, R. M., & Doherty, A. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw220 · Cited by 170 · see citing works
Suh, S., Choi, E. H., Leinonen, H., Foik, A. T., Newby, G. A., Yeh, W.-H., Dong, Z., Kiser, P. D., Lyon, D. C., Liu, D. R., et al. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00632-6 · Cited by 162 · see citing works
Self-citationPan, D., Günther, R., Duan, W., Wendell, S. K., Kaemmerer, W. F., Kafri, T., Verma, I. M., & Whitley, C. B. (2002) · Molecular Therapy · doi:10.1006/mthe.2002.0630 · Cited by 145 · see citing works
Protein transduction from retroviral Gag precursors
Voelkel, C., Galla, M., Maetzig, T., Warlich, E., Kuehle, J., Zychlinski, D., Bode, J., Cantz, T., Schambach, A., & Baum, C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914517107 · Cited by 138 · see citing works
Gesicle-Mediated Delivery of CRISPR/Cas9 Ribonucleoprotein Complex for Inactivating the HIV Provirus
Campbell, L. A., Coke, L. M., Richie, C. T., Fortuno, L. V., Park, A. Y., & Harvey, B. K. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.10.002 · Cited by 134 · see citing works
UDiTaS™, a genome editing detection method for indels and genome rearrangements
Giannoukos, G., Ciulla, D., Marco, E., Abdulkerim, H. S., Barrera, L. A., Bothmer, A., Dhanapal, V., Gloskowski, S. W., Jayaram, H., Maeder, M. L., et al. (2018) · BMC Genomics · doi:10.1186/s12864-018-4561-9 · Cited by 131 · see citing works
Protein Transfer Into Human Cells by VSV-G-induced Nanovesicles
Mangeot, P.-E., Dollet, S., Girard, M., Ciancia, C., Joly, S., Peschanski, M., & Lotteau, V. (2011) · Molecular Therapy · doi:10.1038/mt.2011.138 · Cited by 121 · see citing works
Lyu, P., Javidi-Parsijani, P., Atala, A., & Lu, B. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz605 · Cited by 119 · see citing works
Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation
Meunier, L., & Larrey, D. G. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01482 · Cited by 106 · see citing works
Parr-Brownlie, L., Bosch-Bouju, C., Schoderboeck, L., Sizemore, R. J., Abraham, W., & Hughes, S. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00014 · Cited by 101 · see citing works
Kato, S., Kuramochi, M., Kobayashi, K., Fukabori, R., Okada, K., Uchigashima, M., Watanabe, M., Tsutsui, Y., & Kobayashi, K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4005-11.2011 · Cited by 95 · see citing works
Osborn, M. J., Newby, G. A., McElroy, A. N., Knipping, F., Nielsen, S. C., Riddle, M. J., Xia, L., Chen, W., Eide, C. R., Webber, B. R., et al. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.07.701 · Cited by 94 · see citing works
Self-citationHigh-purity production and precise editing of DNA base editing ribonucleoproteins
Jang, H.-K., Jo, D. H., Lee, S.-N., Cho, C. S., Jeong, Y. K., Jung, Y., Yu, J., Kim, J. H., Woo, J.-S., & Bae, S. (2021) · Science Advances · doi:10.1126/sciadv.abg2661 · Cited by 93 · see citing works
Morphology and ultrastructure of retrovirus particles
Zhang, W., Cao, S., Martin, J. L., Mueller, J. D., & Mansky, L. M. (2015) · AIMS Biophysics · doi:10.3934/biophy.2015.3.343 · Cited by 76 · see citing works
Large-Fragment Deletions Induced by Cas9 Cleavage while Not in the BEs System
Song, Y., Liu, Z., Zhang, Y., Chen, M., Sui, T., Lai, L., & Li, Z. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.06.019 · Cited by 72 · see citing works
Importance of Membrane Structural Integrity for RPE65 Retinoid Isomerization Activity
Golczak, M., Kiser, P. D., Lodowski, D. T., Maeda, A., & Palczewski, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.063941 · Cited by 65 · see citing works
Self-citationWang, D., Shukla, C., Liu, X., Schoeb, T. R., Clarke, L. A., Bedwell, D. M., & Keeling, K. M. (2010) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2009.08.002 · Cited by 62 · see citing works
Jo, D. H., Jang, H., Cho, C. S., Han, J. H., Ryu, G., Jung, Y., Bae, S., & Kim, J. H. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.11.021 · Cited by 61 · see citing works
Rao, A. S., Lindholm, D., Rivas, M. A., Knowles, J. W., Montgomery, S. B., & Ingelsson, E. (2018) · Circulation: Genomic and Precision Medicine · doi:10.1161/circgen.118.002162 · Cited by 60 · see citing works
Retinal transduction profiles by high-capacity viral vectors
Puppo, A., Cesi, G., Marrocco, E., Piccolo, P., Jacca, S., Shayakhmetov, D. M., Parks, R. J., Davidson, B. L., Colloca, S., Brunetti‐Pierri, N., et al. (2014) · Gene Therapy · doi:10.1038/gt.2014.57 · Cited by 58 · see citing works
Lyu, P., Lu, Z., Cho, S.-I., Yadav, M., Yoo, K. W., Atala, A., Kim, J., & Lu, B. (2021) · The CRISPR Journal · doi:10.1089/crispr.2020.0095 · Cited by 48 · see citing works
Indiková, I., & Indik, S. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa561 · Cited by 47 · see citing works
Sodi, A., Banfi, S., Testa, F., Corte, M. D., Passerini, I., Pelo, E., Rossi, S., Simonelli, F., & Italian IRD Working Group (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01868-4 · Cited by 43 · see citing works
Renner, T. M., Tang, V. A., Burger, D. E., & Langlois, M. (2019) · Journal of Virology · doi:10.1128/jvi.01600-19 · Cited by 42 · see citing works
Maximizing lentiviral vector gene transfer in the CNS
Humbel, M., Ramosaj, M., Zimmer, V., Regio, S., Aeby, L., Moser, S., Boizot, A., Sipion, M., Rey, M. J., & Déglon, N. (2020) · Gene Therapy · doi:10.1038/s41434-020-0172-6 · Cited by 41 · see citing works
Fehér, A., Boross, P., Sperka, T., Miklóssy, G., Kádas, J., Bagossi, P., Oroszlan, S., Weber, I., & Tőzsér, J. (2006) · Journal of General Virology · doi:10.1099/vir.0.81382-0 · Cited by 25 · see citing works
MLV based viral-like-particles for delivery of toxic proteins and nuclear transcription factors
Wu, D., & Roth, M. J. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.06.006 · Cited by 23 · see citing works
Johnson, S. N., Wheeler, J. X., Thorpe, R., Collins, M. K., Takeuchi, Y., & Zhao, Y. (2018) · Biologicals · doi:10.1016/j.biologicals.2017.12.005 · Cited by 19 · see citing works
Zhong, Z., Feng, R., Dai, Y., Yibulayin, A., Zeng, L., Liao, J., Wang, L., Huang, Z., Zhou, Z., & Chen, J. (2019) · PubMed Central · Cited by 17 · see citing works
Proteomics analysis of cellular components in lentiviral vector production using Gel‐LC‐MS/MS
Wheeler, J. X., Jones, C., Thorpe, R., et al. (2007) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200600522 · Cited by 12 · see citing works
Jo, D. H., Jang, H., Cho, C. S., Han, J. H., Ryu, G., Jung, Y., Bae, S., & Kim, J. H. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.07.425822 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Past, present, and future of CRISPR genome editing technologies
Pacesa, M., Pelea, O., & Jinek, M. (2024) · Cell · doi:10.1016/j.cell.2024.01.042 · Cited by 609 · see citing works
UM171 glues asymmetric CRL3–HDAC1/2 assembly to degrade CoREST corepressors
Yeo, M. J. R., Zhang, O., Xie, X., Nam, E., Payne, N. C., Gosavi, P. M., Kwok, H. S., Iram, I., Lee, C., Li, J., et al. (2025) · Nature · doi:10.1038/s41586-024-08532-4 · Cited by 58 · see citing works
Ren, D., Fisson, S., Dalkara, D., & Ail, D. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091973 · Cited by 52 · see citing works
Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations
Xie, X., Zhang, O., Yeo, M. J. R., Lee, C., Tao, R., Harry, S. A., Payne, N. C., Nam, E., Paul, L., Li, Y., et al. (2025) · Nature · doi:10.1038/s41586-024-08533-3 · Cited by 50 · see citing works
Adeno-Associated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We?
Ail, D., Malki, H., Zin, E. A., & Dalkara, D. (2023) · The Application of Clinical Genetics · doi:10.2147/tacg.s383453 · Cited by 40 · see citing works
Shen, Q., Ruan, H., Zhang, H., Wu, T., Zhu, K., Han, W., Dong, R., Ming, T., Qi, H., & Zhang, Y. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1375120 · Cited by 38 · see citing works
Salman, A., Kantor, A., McClements, M. E., Marfany, G., Trigueros, S., & MacLaren, R. E. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091842 · Cited by 37 · see citing works
Nanoblades allow high-level genome editing in murine and human organoids
Tiroille, V., Krug, A., Bokobza, E., Kahi, M., Bulcaen, M., Ensinck, M. M., Geurts, M. H., Hendriks, D., Vermeulen, F., Larbret, F., et al. (2023) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2023.06.004 · Cited by 25 · see citing works
Carvalho, C., Lemos, L., Antas, P., & Seabra, M. C. (2023) · Frontiers in Ophthalmology · doi:10.3389/fopht.2023.1270561 · Cited by 21 · see citing works
Pulman, J., Botto, C., Malki, H., Ren, D., Oudin, P., De Cian, A., As, M., Izabelle, C., Saubamea, B., Forster, V., et al. (2024) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2024.102349 · Cited by 12 · see citing works
Eaton, E. J., Wick, B. J., Chacón, J. S., Wang, A. J., Kluesner, M., Barnes, J. T., Kar, B., Wang, M., Johnson, M. J., Skeate, J. G., et al. (2026) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2026.102908 · Cited by 2 · see citing works
Siles, L., Ruiz-Nogales, S., Méndez-Vendrell, P., & Pomares, E. (2026) · Cells · doi:10.3390/cells15050457
“Regarding ocular diseases, several studies investigated the feasibility of base-editors and gene editing in murine models [28,29].”
- Authors
- Banskota, S., Raguram, A., Suh, S., Du, S. W., Davis, J. R., Choi, E. H., Wang, X., Nielsen, S. C., Newby, G. A., Randolph, P. B., Osborn, M. J., Musunuru, K., Palczewski, K., & Liu, D. R.
- Affiliations
- Broad Institute (US)
- University of California, Irvine (US)
- University of Pennsylvania (US)
- University of Minnesota (US)
- Corresponding author
- Liu, David R.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 185
- Issue
- 2
- Pages
- 250-265.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8809250
- OpenAlex
- W4206390074
- Cited by
- 668
- References
- 92
- Citations by year
- 2026: 162 · 2025: 158 · 2024: 129 · 2023: 137 · 2022: 81 · 2012: 1
- FWCI
- 41.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- NIH (RM1HG009490, U01AI142756, UG3AI150551, R35GM118062, R01EY009339)
- National Science Foundation (T32EY024236, F30EY029136, T32GM007250, T32GM008620)
- Bill & Melinda Gates Foundation
- Helen Hay Whitney Foundation
- Howard Hughes Medical Institute (T32GM095450)
- Broad Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- base editing, Cas9 ribonucleoprotein, cell tropism, PCSK9, off-target editing, non-viral vectors
- MeSH terms
- Proprotein Convertase 9, Gene Editing, Animals, Base Sequence, Blindness, Brain, Disease Models, Animal, DNA, Fibroblasts, Genetic Engineering, Humans, Liver, Mice, Inbred C57BL, Proteins, Retroviridae, Virion, Vision, Ocular, Drug Delivery Systems, Mice, Retinal Pigment Epithelium, HEK293 Cells
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.
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