Non-viral Delivery of Zinc Finger Nuclease mRNA Enables Highly Efficient In Vivo Genome Editing of Multiple Therapeutic Gene Targets
Open accessAbstract
It has previously been shown that engineered zinc finger nucleases (ZFNs) can be packaged into adeno-associated viruses (AAVs) and delivered intravenously into mice, non-human primates, and most recently, humans to induce highly efficient therapeutic genome editing in the liver. Lipid nanoparticles (LNPs) are synthetic delivery vehicles that enable repeat administration and are not limited by the presence of preexisting neutralizing antibodies in patients. Here, we show that mRNA encoding ZFNs formulated into LNP can enable >90% knockout of gene expression in mice by targeting the TTR or PCSK9 gene, at mRNA doses 10-fold lower than has ever been reported. Additionally, co-delivering mRNA-LNP containing ZFNs targeted to intron 1 of the ALB locus with AAV packaged with a promoterless human IDS or FIX therapeutic transgene can result in high levels of targeted integration and subsequent therapeutically relevant levels of protein expression in mice. Finally, we show repeat administration of ZFN mRNA-LNP after a single AAV donor dose results in significantly increased levels of genome editing and transgene expression compared to a single dose. These results demonstrate LNP-mediated ZFN mRNA delivery can drive highly efficient levels of in vivo genome editing and can potentially offer a new treatment modality for a variety of diseases.
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Gene-editing components can be delivered by lipid nanoparticle-mRNA formulations to treat genetic diseases, including hereditary tyrosinaemia type I, hypercholesterolaemia, lipoprotein metabolism disorders and transthyretin amyloidosis, as demonstrated in preclinical studies.
“Gene-editing components can be delivered by lipid nanoparticle–mRNA formulations to treat genetic diseases, including HTI92,238, hypercholesterolaemia81,96,105,239, lipoprotein metabolism disorders85 and transthyretin amyloidosis239,240, which has been demonstrated in preclinical studies.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [239]
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In vivo cytidine base editing of hepatocytes without detectable off-target mutations in RNA and DNA
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“New technologies to enhance the efficiency of gene editing while maintaining safety and specificity are emerging, including incorporation of ZFN structures into lipid nanoparticles (42) and improvement of ZFN structure algorithms that are able to generate ZFNs with a higher degree of precision, efficiency, and specifi…”
BackgroundSelf-citationsiRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases
Kalita, T., Dezfouli, S. A., Pandey, L. M., & Uludağ, H. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14112520 · Cited by 87 · see citing works
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Optimizing synthetic nucleic acid and protein nanocarriers: The chemical evolution approach
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Lipid Nanoparticle Delivery Systems to Enable mRNA-Based Therapeutics
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“Encapsulating Zinc finger nucleases ZFN-mRNA in LNP were reported to enable >90% knockdown of TTR or PCSK9 gene [79] while the delivery of MEGA-TAL-mRNA also delivered with LNP resulted in up to 60% INDEL, which also corresponded to high levels (80%) of PCSK9 suppression and reduction in total cholesterol (Moore et 20…”
BackgroundSelf-citationPrecise genome-editing in human diseases: mechanisms, strategies and applications
Zheng, Y., Li, Y., Zhou, K., Li, T., VanDusen, N. J., & Hua, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01750-2 · Cited by 80 · see citing works
mRNA – A game changer in regenerative medicine, cell-based therapy and reprogramming strategies
Chabanovska, O., Galow, A.-M., David, R., & Lemcke, H. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114002 · Cited by 76 · see citing works
“LNP-loaded mod-mRNA is predominantly metabolized in the liver when applied intravenously [261,262].”
BackgroundGene editing and its applications in biomedicine
Li, G., Li, X., Zhuang, S., Wang, L., Zhu, Y., Chen, Y., Sun, W. C., Wu, Z., Zhou, Z. L., Chen, J., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2057-0 · Cited by 65 · see citing works
“Soon after Ding’s promising results, this strategy’s long-term efficacy and safety issues were further studied in mice and nonhuman primates via different programmable nucleases, including ZFN (Conway et al., 2019) or meganucleases (Wang et al., 2018b).”
BackgroundDelivery of mRNA for regulating functions of immune cells
Shi, J. Y., Huang, M., Lu, Z.-D., Du, X., Shen, S., Xu, C., & Wang, J. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.033 · Cited by 62 · see citing works
“502 efficiency in Kupffer cells and endothelial cells was approximately 60% [136].”
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Application of lipid-based nanoparticles in cancer immunotherapy
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In the business of base editors: Evolution from bench to bedside
Porto, E. M., & Komor, A. C. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002071 · Cited by 50 · see citing works
Nanotheranostics against COVID-19: From multivalent to immune-targeted materials
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“mRNA-lipid NPs enable durable and highly-efficient editing or silencing the target genes [136,137].”
Nanoscale delivery platforms for RNA therapeutics: Challenges and the current state of the art
Rhym, L. H., & Anderson, D. G. (2022) · Med · doi:10.1016/j.medj.2022.02.001 · Cited by 45 · see citing works
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Correction of Airway Stem Cells: Genome Editing Approaches for the Treatment of Cystic Fibrosis
King, N. E., Suzuki, S., Barillà, C., Hawkins, F. J., Randell, S. H., Reynolds, S. D., Stripp, B. R., & Davis, B. R. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.160 · Cited by 40 · see citing works
New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery
Niculescu, A.-G., Bîrcă, A. C., & Grumezescu, A. M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122053 · Cited by 39 · see citing works
“mRNA has also been evaluated for cardiovascular conditions, with several LNP-based formulations being tested for enhancing cardiac function and regeneration [46], reducing LDL-C levels [47], and treating endotheliopathy associated with vascular senescence [48,49].”
BackgroundTargeted Gene Delivery: Where to Land
Pavani, G., & Amendola, M. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2020.609650 · Cited by 40 · see citing works
“Until today, this strategy has been successfully applied in different preclinical models of hemophilia A and B (Barzel et al., 2015; Sharma et al., 2015; Chen et al., 2019; Conway et al., 2019; Zhang et al., 2019; Wang Q. et al., 2020) and metabolic disorders (Laoharawee et al.”
BackgroundMethodTreatment of a metabolic liver disease in mice with a transient prime editing approach
Rothgangl, T., Tálas, A., Ioannidi, E. I., Weber, Y., Böck, D., Matsushita, M., Villiger, E. A., Schmidheini, L., Moon, W. J., Lin, P. J. C., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01399-4 · Cited by 43 · see citing works
Self-citationDare to Compare. Development of Atherosclerotic Lesions in Human, Mouse, and Zebrafish
Vedder, V. L., Aherrahrou, Z., & Erdmann, J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00109 · Cited by 30 · see citing works
Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders
Arjunan, P., Kathirvelu, D., Mahalingam, G., Goel, A., Zacharaiah, U. G., Srivastava, A., & Marepally, S. K. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.04.015 · Cited by 31 · see citing works
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mRNA delivery technologies: Toward clinical translation
Gómez-Aguado, I., Rodríguez-Castejón, J., Beraza-Millor, M., Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., & Solinís, M. Á. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.010 · Cited by 23 · see citing works
Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy
Mashima, R., & Nakanishi, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158153 · Cited by 20 · see citing works
Wang, H., Tang, L. Y., Kong, Y., Liu, W., Zhu, X., & You, Y. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119115 · Cited by 19 · see citing works
“Lipid nanoparticles (LNPs) are also used to deliver zinc finger nuclease mRNA into cells for gene editing [105].”
BackgroundEly, A., Singh, P., Smith, T. S., & Arbuthnot, P. B. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.05.010 · Cited by 19 · see citing works
Preclinical Assessment of a Gene Editing Approach in a Mouse Model of MNGIE
Parés, M., Fornaguera, C., Vila‐Julià, F., Oh, S., Fan, S. H. Y., Tam, Y. K., Comes, N., Vidal, F., Martí, R., Borrós, S., et al. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.152 · Cited by 17 · see citing works
Self-citationGenome editing technologies to treat rare liver diseases
Trevisan, M., Masi, G., & Palù, G. (2020) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2019.10.10 · Cited by 16 · see citing works
“This lipid-based delivery system has been applied also for the delivery of a PCSK9-targeted ZFNsmRNAs, resulting in 90% reduction of protein plasma levels (72).”
MethodMuto, H., Kubara, K., Hitaoka, S., Osada, Y., & Suzuki, Y. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114055 · Cited by 17 · see citing works
Liver-directed gene-based therapies for inborn errors of metabolism
Piccolo, P., Rossi, A., & Brunetti‐Pierri, N. (2020) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2020.1817375 · Cited by 16 · see citing works
Stone, D., Takeuchi, R., Dulin, H., Loprieno, M. A., Strongin, D. E., Sathees, S., Cradick, T. J., Aubert, M., Roychoudhury, P., Gordon, J., et al. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101470 · Cited by 15 · see citing works
Advances in Development of mRNA-Based Therapeutics
Huang, L., Zhang, L., Li, W., Li, S., Wen, J., Li, H., & Liu, Z. (2020) · Current topics in microbiology and immunology · doi:10.1007/82_2020_222 · Cited by 14 · see citing works
Self-citationOrganic Nanoparticles in Progressing Cardiovascular Disease Treatment and Diagnosis
Scafa‐Udriște, A., Burdușel, A.-C., Niculescu, A.-G., Rădulescu, M., Balaure, P. C., & Grumezescu, A. M. (2024) · Polymers · doi:10.3390/polym16101421 · Cited by 15 · see citing works
“…materials, and their morphology is comparable to cell membranes [33]. can include hydrophilic and lipophilic materials, and their morphology is comparable They have effectively displayed the capacity to introduce a variety of biomaterials, including peptides, proteins, nucleic acids, imaging”
BackgroundGarcia, D. A., Pierre, A. F., Quirino, L., Acharya, G., Vasudevan, A., Pei, Y., Chung, E., Chang, J. Y. H., Lee, S., Endow, M., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.11.020 · Cited by 13 · see citing works
“27 For example, the fi rst LNP-based CRISPR-Cas9 in vivo gene editingtherapywasrecentlytestedinhumansfortherarediseasehered-itary transthyretin amyloidosis, or hATTR.”
The significance of bioengineered nanoplatforms against SARS-CoV-2: From detection to genome editing
Hassanzadeh, P. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119289 · Cited by 13 · see citing works
“mRNA-lipid NPs which code for the programmable nucleases enable highly-efficient and persistent genome editing of several gene targets in vivo [180].”
Research progress of mRNA vaccines for infectious diseases
Zhang, Z., Du, J., Zhang, D., Han, R., Wu, X., & Liang, Y. (2025) · European journal of medical research · doi:10.1186/s40001-025-03060-x · Cited by 16 · see citing works
“…such as DLin-MC3-DMA L319 [80], C12-200 and cKK-E12 [81–83], ALC-0315, and SM-102, which are used in COVID-19 vaccines [84], TT3 and its biode-gradable derivative FTT5 [84, 85], vitamin-derived lipids ssPalmE [86] and VcLNP [87], A9 [88], L5 [89], A18 Lipid [90], ATX Lipid [91] and LP01 [92].”
Unlocking mRNA-driven CRISPR-Cas9 gene therapy via optimizing mRNA and the delivery vectors
Wang, S., Xu, X., Viitala, T., Shu, Y., & Zhang, H. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102737 · Cited by 11 · see citing works
“8,172,173 The Moderna and BioNTech/Pfizer COVID-19 vaccines mRNA-1273 and BNT162B2 also utilized ionizable cationic lipids (e.g., Dlin-MC3-DMA and ALC-0135, respectively) in their LNP formulations.”
Immunotherapy and Gene Therapy for Oncoviruses Infections: A Review
de Almeida, N. A. A., Ribeiro, C. R. D. A., Raposo, J. V., & de Paula, V. S. (2021) · Viruses · doi:10.3390/v13050822 · Cited by 11 · see citing works
Polyglutamine spinocerebellar ataxias: emerging therapeutic targets
Neves‐Carvalho, A., Duarte‐Silva, S., Teixeira‐Castro, A., & Maciel, P. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1827394 · Cited by 11 · see citing works
Lipid-based Non-viral Vector: Promising Approach for Gene Delivery
Panday, A., Dixena, B., Jain, N. S., & Jain, A. K. (2024) · Current Pharmaceutical Design · doi:10.2174/0113816128324084240828084904 · Cited by 10 · see citing works
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“The ionizable cationic lipid used in our study is described in patent CN2025110953219 and its structural formula is based on previous studies 33,34 .”
Li, Z.-F., & Wu, N. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.911429 · Cited by 10 · see citing works
“Besides, this method was well tolerated and efficient genome editing continuously increased after repeated dosing (Conway et al., 2019).”
MethodHematopoietic stem and progenitors cells gene editing: Beyond blood disorders
Buffa, V., Vargas, J. R. A., Galy, A. H. M., Spinozzi, S., & Rocca, C. J. (2023) · Frontiers in Genome Editing · doi:10.3389/fgeed.2022.997142 · Cited by 9 · see citing works
“Delivery of transcribed mRNA coding for ZFN (DiGiusto et al., 2016; Conway et al., 2019), TALEN (Lux et al., 2019) and CRISPR-Cas9 (Hendel et al., 2015) into HSPCs showed great promises in terms of efficacy and safety.”
BackgroundMak, M. C. E., Gurung, R., & Foo, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814057 · Cited by 10 · see citing works
Liver gene transfer for metabolite detoxification in inherited metabolic diseases
D’Alessio, A. M., Boffa, I., Stefano, L. D., Soria, L. R., & Brunetti‐Pierri, N. (2024) · FEBS Letters · doi:10.1002/1873-3468.14957 · Cited by 8 · see citing works
Present and future of lipid nanoparticle-mRNA technology in phenylketonuria disease treatment
Dı́az-Trelles, R., & Pérez‐García, C. G. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.008 · Cited by 8 · see citing works
Treating Cardiovascular Disease with Liver Genome Engineering
Hurley, A. E., & Lagor, W. R. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-00986-z · Cited by 7 · see citing works
Gene editing in liver diseases
Torella, L., Santana‐Gonzalez, N., Zabaleta, N., & González‐Aseguinolaza, G. (2024) · FEBS Letters · doi:10.1002/1873-3468.14989 · Cited by 7 · see citing works
“An alternative approach to ZFN is the use of CRISPR/Cas9 in a dual AAV system: an AAV carrying CRISPR-Cas9 targeting the Alb locus and an AAV carrying the therapeutic template [78].”
CRISPR/Cas9 Editing: Sparking Discussion on Safety in Light of the Need for New Therapeutics
Carlaw, T., Zhang, L., & Ross, C. J. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.111 · Cited by 7 · see citing works
Self-citationA Decade of Genome Editing: Comparative Review of ZFN, TALEN, and CRISPR/Cas9
Kumar, R., Bargoti, T., Sengar, S., Singh, D., & Nain, V. (2025) · doi:10.38124/ijisrt/25apr2221 · Cited by 5 · see citing works
Corrigendum: Targeted Gene Delivery: Where to Land
Pavani, G., & Amendola, M. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.682171 · Cited by 5 · see citing works
“…Extensive validation required Barzel et al., 2015; Sharma et al., 2015; Davidoff and Nathwani, 2016; Laoharawee et al., 2018; Chen et al., 2019; Conway et al., 2019; De Caneva et al., 2019; Ou et al., 2019, 2020; Zhang et al., 2019; Wang Q. et al., 2020 C Tolerant to integration (AAVS1, CCR5,…”
BackgroundTreatment of a genetic liver disease in mice through transient prime editor expressionPreprint
Rothgangl, T., Ioannidi, E. I., Weber, Y., Tálas, A., Böck, D., Matsushita, M., Villiger, E. A., Schmidheini, L., Moon, J., Lin, P. J. C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.22.575834 · Cited by 5 · see citing works
“LNP were formulated as described previously 53 .”
MethodSelf-citationLi, W., Wang, C., & Lu, Y. (2024) · Nano Research · doi:10.1007/s12274-024-6729-8 · Cited by 4 · see citing works
Therapeutic applications of gene editing in chronic liver diseases: an update
Shin, J. H., Lee, J., Jung, Y. K., Kim, K. S., Jeong, J., & Choi, D. (2022) · BMB Reports · doi:10.5483/bmbrep.2022.55.6.033 · Cited by 4 · see citing works
“A similar strategy was adopted by delivering ZFNs mRNAs using lipid nanoparticles (LNPs), which are not limited by the pre-existing neutralizing antibodies (25).”
BackgroundMethodSelf-citationBobis‐Wozowicz, S., Kania, K., Nit, K., Błażowska, N., Kmiotek‐Wasylewska, K., Paw, M., Karnas, E., Szyposzyńska, A., Tyszka‐Czochara, M., Woźnicka, O., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.25.432823 · Cited by 4 · see citing works
“Importantly, genetic inactivation of Pcsk9 gene in the animal livers using engineered meganucleases [50], ZFN [51], base editors [52], or chemically improved gRNA/Cas9 complexes [53] resulted in persistent reduction of serum cholesterol, highlighting long-term benefits of a gene therapy approach.”
BackgroundSpatial profiling of gene editing by in situ sequencing in mice and macaques
Janjuha, S., Haenggi, T., Chamberlain, T. C., Rothgangl, T., Kissling, L., Wilhelm, M., Mathis, N., Böck, D., Marquart, K. F., Ioannidi, E. I., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01512-7 · Cited by 3 · see citing works
“The mRNA-LNP was formulated as described previously 47 .”
Self-citationApplications of genome editing technologies in the treatment of human diseases
Alshorman, J., Mehran, M. J., Tembo, K. M., Mostafavi, N., Bolideei, M., & Wang, Y. L. (2026) · Gene Therapy · doi:10.1038/s41434-026-00627-z · Cited by 3 · see citing works
Application of Gene Editing Technology Based on Targeted Delivery Materials in TNBC
Qu, P., Li, X., Liu, J., Su, X., Han, S., Wang, Y., Luo, Y., Li, J., Ma, C., Deng, S., et al. (2025) · ACS Omega · doi:10.1021/acsomega.5c01294 · Cited by 3 · see citing works
Zinc finger proteins (ZFPs) in health and disease
Zhao, Z., Huang, K., Liao, Z., Chen, B., Chen, J., & Mei, Z. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00413-8 · Cited by 2 · see citing works
Zinc Finger Proteins as Regulators of Organ Fibrosis
Boonkaew, B., Srivongtrakul, W., & Ariyachet, C. (2026) · Journal of Cellular Biochemistry · doi:10.1002/jcb.70103 · Cited by 1 · see citing works
“Genome engineering platforms, including zinc finger nucleases and programmable transcription factors, enable precise modulation of gene expression and fibrotic pathways [166, 167].”
COVID-19 and progress in therapeutic approaches: a narrative review
Ilyas, U., Jadoon, S. S., Ahmed, T., Altaf, R., Khan, A., Ahmad, A., Rasool, Y., Masaud, S. M., & Khan, Z. (2024) · Çukurova medical journal (Online)/Çukurova medical journal · doi:10.17826/cumj.1394329 · Cited by 1 · see citing works
Genome editing in lysosomal disorders
Pimentel-Vera, L. N., Poletto, É., Gonzalez, E. A., Poswar, F. D. O., Giugliani, R., & Baldo, G. (2021) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2021.02.001 · Cited by 1 · see citing works
Lipid nanoparticles for delivery of gene editing components
Kang, D. D., & Dong, Y. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822425-0.00096-8 · Cited by 1 · see citing works
Delivery and Formulation Methods for Therapeutic Genome Editing
Blenke, E. O., & Krishnamurthy, V. R. (2022) · Wiley eBooks · doi:10.1002/9781119671404.ch18
Messenger RNA Therapeutics: Start of a New Era in Medicine
Jain, S., George, A. J., Sharma, V., Singh, G., & Gupta, V. (2022) · RNA technologies · doi:10.1007/978-3-031-08415-7_3
Establishment of FUT8 gene knockout CHO cell line with stable expression of monoclonal antibodyPreprint
Gao, L., Zhang, M., Li, B., Zhang, C., Miao, X., Li, X., Yu, C., & Li, H. (2023) · Research Square · doi:10.21203/rs.3.rs-3691208/v1
Shaikh, S. (2024) · Springer eBooks · doi:10.1007/978-981-97-7292-6_23
Zhu, Y., You, G., Jiang, Y., Yin, K., Wang, R., Li, C., Zhang, X., Yan, Z., Ding, M., Guo, W., et al. (2025) · The FASEB Journal · doi:10.1096/fj.202502602r
“Similarly, rAAV-or LNP-packaged zinc finger nucleases (ZFNs) achieve safe and high-efficiency liver genome editing [21].”
Self-citationRole of gene therapy and immunotherapy in precision medicine
Khan, I. A., Khatun, H., & Viswa, P. D. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33302-6.00011-1
Biogenic Nanoparticles in Cardiovascular Disease: Current Insights and Future Prospects
Diallo, F., Niang, T., Seck, I., Sokhna, S., Ndao, M., Ndoye, S. F., Ciss, I., Ba, L. A., Seck, M., & Nguemo, F. (2026) · Advances in Nanoparticles · doi:10.4236/anp.2026.151001
Gene therapy for liver diseases: methods, challenges and opportunities
Yan, M., & Xiang, Q. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04518-8
“Encapsulation of ZFN-encoding mRNA within LNPs, targeting either the TTR or PCSK9 gene results in a reduction of the respective protein expression by over 90% in mice, offering potential therapeutic applications for transthyretin amyloidosis and hypercholesterolemia, respectively [338].”
Tálas, A., Ioannidi, E. I., Weber, Y., Haenggi, T., Kulcsár, P. I., Zürcher, N., Faccin, E., Moon, W. J., Kissling, L., Villiger, E. A., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.aec7274
Self-citationAdvances in RNA-Based Therapeutics in Oncology
Lopes-Cardoso, H., Panão-Costa, J., Amaral, A. T., Soares-Gonçalves, J., Neves, B. F., Voronovska, A., Batista, A., Biscaia-Caleiras, M., Fonseca, N. A., Simões, S., et al. (2026) · Springer handbooks · doi:10.1007/978-3-032-01636-2_19
Zeng, Y., Song, T., Liu, S., Liao, X., Hu, M., Yang, H., He, S., & Song, X. (2026) · Chinese Medical Journal BioMed · doi:10.65457/cmjbm-2026-0005
Rewiring cellular immunotherapy: From CAR evolution to circuit innovations across diseases
Chen, J., Cui, Y., Du, K., Liu, J., Xie, J., Wang, S., & Yang, Z. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.108980
- Authors
- Conway, A., Mendel, M., Kim, K., McGovern, K., Boyko, A., Zhang, L., Miller, J. C., DeKelver, R. C., Paschon, D. E., Mui, B. L., Lin, P. J. C., Tam, Y. K., Barbosa, C., Redelmeier, T., Holmes, M. C., & Lee, G.
- Affiliations
- Sangamo BioSciences (United States) (US)
- Acuitas Therapeutics (Canada) (CA)
- Corresponding author
- Conway, Anthony
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 27
- Issue
- 4
- Pages
- 866-877
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC6453547
- OpenAlex
- W2921219680
- Cited by
- 95
- References
- 55
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 13 · 2023: 10 · 2022: 16 · 2021: 18 · 2020: 17 · 2019: 1
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sangamo Therapeutics
- 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
- zinc finger nucleases, mRNA delivery, lipid nanoparticles, non-viral gene delivery, in vivo gene editing, adeno-associated virus vectors, PCSK9, alpha-1-antitrypsin, IDS, factor IX, liver-directed gene therapy, transgene expression
- MeSH terms
- Proprotein Convertase 9, Gene Editing, Zinc Finger Nucleases, Dependovirus, Animals, Cells, Cultured, Female, Genetic Vectors, Introns, Lipids, Male, Mice, Inbred C57BL, Prealbumin, RNA, Messenger, Drug Delivery Systems, Transgenes, Hepatocytes, Mice, Nanoparticles, Gene Knockout Techniques
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 ›
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