Lipid-coated mesoporous silica nanoparticles for anti-viral applications via delivery of CRISPR-Cas9 ribonucleoproteins

LaBauve, Annette E.; Saada, Edwin A.; Jones, Iris K. A.; Mosesso, Richard; Noureddine, Achraf; Techel, Jessica; Gomez, Andrew; Collette, Nicole; Sherman, Michael B.; Serda, Rita E.; Butler, Kimberly S.; Brinker, C. Jeffery; Schoeniger, Joseph S.; Sasaki, Darryl; Negrete, Oscar A.

doi:10.1038/s41598-023-33092-4

Title: Lipid-coated mesoporous silica nanoparticles for anti-viral applications via delivery of CRISPR-Cas9 ribonucleoproteins

Journal Article · 27 April 2023 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-023-33092-4 · OSTI ID:1971675

LaBauve, Annette E.; Saada, Edwin A.; Jones, Iris K. A.; Mosesso, Richard; Noureddine, Achraf; Techel, Jessica; Gomez, Andrew; Collette, Nicole; Sherman, Michael B.; Serda, Rita E.; Butler, Kimberly S.; Brinker, C. Jeffery; Schoeniger, Joseph S.; Sasaki, Darryl; Negrete, Oscar A.

Abstract Emerging and re-emerging viral pathogens present a unique challenge for anti-viral therapeutic development. Anti-viral approaches with high flexibility and rapid production times are essential for combating these high-pandemic risk viruses. CRISPR-Cas technologies have been extensively repurposed to treat a variety of diseases, with recent work expanding into potential applications against viral infections. However, delivery still presents a major challenge for these technologies. Lipid-coated mesoporous silica nanoparticles (LCMSNs) offer an attractive delivery vehicle for a variety of cargos due to their high biocompatibility, tractable synthesis, and amenability to chemical functionalization. Here, we report the use of LCMSNs to deliver CRISPR-Cas9 ribonucleoproteins (RNPs) that target the Niemann–Pick disease type C1 gene, an essential host factor required for entry of the high-pandemic risk pathogen Ebola virus, demonstrating an efficient reduction in viral infection. We further highlight successful in vivo delivery of the RNP-LCMSN platform to the mouse liver via systemic administration.

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Research Organization:: Sandia National Laboratories (SNL-CA), Livermore, CA (United States)

Sponsoring Organization:: Defense Advanced Research Projects Agency (DARPA); USDOE; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: NA0003525

OSTI ID:: 1971675

Report Number(s):: SAND--2023-08995J; 6873; PII: 33092

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 13; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (39)

Sol–Gel‐Based Advanced Porous Silica Materials for Biomedical Applications Lei, Qi; Guo, Jimin; Noureddine, Achraf Advanced Functional Materials, Vol. 30, Issue 41 https://doi.org/10.1002/adfm.201909539	journal	April 2020
Protocells: Modular Mesoporous Silica Nanoparticle-Supported Lipid Bilayers for Drug Delivery Butler, Kimberly S.; Durfee, Paul N.; Theron, Christophe Small, Vol. 12, Issue 16 https://doi.org/10.1002/smll.201502119	journal	January 2016
Engineering of large-pore lipid-coated mesoporous silica nanoparticles for dual cargo delivery to cancer cells Noureddine, Achraf; Hjelvik, Elizabeth A.; Croissant, Jonas G. Journal of Sol-Gel Science and Technology, Vol. 89, Issue 1 https://doi.org/10.1007/s10971-018-4772-1	journal	August 2018
Species-specific immunogenicity and protective efficacy of a vesicular stomatitis virus-based Sudan virus vaccine: a challenge study in macaques Marzi, Andrea; Fletcher, Paige; Feldmann, Friederike The Lancet Microbe, Vol. 4, Issue 3 https://doi.org/10.1016/S2666-5247(23)00001-0	journal	March 2023
Engineering of monosized lipid-coated mesoporous silica nanoparticles for CRISPR delivery Noureddine, Achraf; Maestas-Olguin, Angelea; Saada, Edwin A. Acta Biomaterialia, Vol. 114 https://doi.org/10.1016/j.actbio.2020.07.027	journal	September 2020
The role of the helper lipid dioleoylphosphatidylethanolamine (DOPE) for DNA transfection cooperating with a cationic lipid bearing ethylenediamine Mochizuki, Shinichi; Kanegae, Naho; Nishina, Koichi Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1828, Issue 2 https://doi.org/10.1016/j.bbamem.2012.10.017	journal	February 2013
DOTAP/DOPE ratio and cell type determine transfection efficiency with DOTAP-liposomes Kim, Bieong-Kil; Hwang, Guen-Bae; Seu, Young-Bae Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1848, Issue 10 https://doi.org/10.1016/j.bbamem.2015.06.020	journal	October 2015
Recent trends of mesoporous silica-based nanoplatforms for nanodynamic therapies Xu, Qingqing; Yang, Yuanqi; Lu, Junya Coordination Chemistry Reviews, Vol. 469 https://doi.org/10.1016/j.ccr.2022.214687	journal	October 2022
Advances in smart mesoporous carbon nanoplatforms for photothermal–enhanced synergistic cancer therapy Feng, Shuaipeng; Lu, Junya; Wang, Kaili Chemical Engineering Journal, Vol. 435 https://doi.org/10.1016/j.cej.2022.134886	journal	May 2022
Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing Nuñez, James K.; Chen, Jin; Pommier, Greg C. Cell, Vol. 184, Issue 9 https://doi.org/10.1016/j.cell.2021.03.025	journal	April 2021
A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing Finn, Jonathan D.; Smith, Amy Rhoden; Patel, Mihir C. Cell Reports, Vol. 22, Issue 9 https://doi.org/10.1016/j.celrep.2018.02.014	journal	February 2018
Host directed therapies: COVID-19 and beyond Tripathi, Devavrat; Sodani, Megha; Gupta, Pramod Kumar Current Research in Pharmacology and Drug Discovery, Vol. 2 https://doi.org/10.1016/j.crphar.2021.100058	journal	January 2021
Immunocompromised Cas9 transgenic mice for rapid in vivo assessment of host factors involved in highly pathogenic virus infection Collette, Nicole; Dhungel, Pragyesh; Lund, Sean J. Molecular Therapy - Methods & Clinical Development, Vol. 23 https://doi.org/10.1016/j.omtm.2021.09.012	journal	December 2021
Versatile High-Throughput Fluorescence Assay for Monitoring Cas9 Activity Seamon, Kyle J.; Light, Yooli K.; Saada, Edwin A. Analytical Chemistry, Vol. 90, Issue 11 https://doi.org/10.1021/acs.analchem.8b01155	journal	April 2018
In Vivo Delivery of CRISPR/Cas9 for Therapeutic Gene Editing: Progress and Challenges Mout, Rubul; Ray, Moumita; Lee, Yi-Wei Bioconjugate Chemistry, Vol. 28, Issue 4 https://doi.org/10.1021/acs.bioconjchem.7b00057	journal	March 2017
Robust and Long-Term Cellular Protein and Enzymatic Activity Preservation in Biomineralized Mammalian Cells Guo, Jimin; Amini, Shahrouz; Lei, Qi ACS Nano, Vol. 16, Issue 2 https://doi.org/10.1021/acsnano.1c08103	journal	February 2022
Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells Durfee, Paul N.; Lin, Yu-Shen; Dunphy, Darren R. ACS Nano, Vol. 10, Issue 9 https://doi.org/10.1021/acsnano.6b02819	journal	July 2016
Facile Large-Scale Synthesis of Monodisperse Mesoporous Silica Nanospheres with Tunable Pore Structure Zhang, Kun; Xu, Lang-Lang; Jiang, Jin-Gang Journal of the American Chemical Society, Vol. 135, Issue 7 https://doi.org/10.1021/ja3116873	journal	February 2013
Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity Lin, Yu-Shen; Haynes, Christy L. Journal of the American Chemical Society, Vol. 132, Issue 13 https://doi.org/10.1021/ja910846q	journal	April 2010
Ebola virus entry requires the cholesterol transporter Niemann–Pick C1 Carette, Jan E.; Raaben, Matthijs; Wong, Anthony C. Nature, Vol. 477, Issue 7364 https://doi.org/10.1038/nature10348	journal	August 2011
Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo Zuris, John A.; Thompson, David B.; Shu, Yilai Nature Biotechnology, Vol. 33, Issue 1 https://doi.org/10.1038/nbt.3081	journal	October 2014
Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes Staahl, Brett T.; Benekareddy, Madhurima; Coulon-Bainier, Claire Nature Biotechnology, Vol. 35, Issue 5 https://doi.org/10.1038/nbt.3806	journal	February 2017
A multifunctional AAV–CRISPR–Cas9 and its host response Chew, Wei Leong; Tabebordbar, Mohammadsharif; Cheng, Jason K. W. Nature Methods, Vol. 13, Issue 10 https://doi.org/10.1038/nmeth.3993	journal	September 2016
CRISPR interference (CRISPRi) for sequence-specific control of gene expression Larson, Matthew H.; Gilbert, Luke A.; Wang, Xiaowo Nature Protocols, Vol. 8, Issue 11 https://doi.org/10.1038/nprot.2013.132	journal	October 2013
Host-directed therapies for bacterial and viral infections Kaufmann, Stefan H. E.; Dorhoi, Anca; Hotchkiss, Richard S. Nature Reviews Drug Discovery, Vol. 17, Issue 1 https://doi.org/10.1038/nrd.2017.162	journal	September 2017
Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing Wei, Tuo; Cheng, Qiang; Min, Yi-Li Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-17029-3	journal	June 2020
Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing Cheng, Qiang; Wei, Tuo; Farbiak, Lukas Nature Nanotechnology, Vol. 15, Issue 4 https://doi.org/10.1038/s41565-020-0669-6	journal	April 2020
Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection Cui, Zhifen; Zeng, Cong; Huang, Furong Nature Chemical Biology, Vol. 18, Issue 10 https://doi.org/10.1038/s41589-022-01094-4	journal	July 2022
Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection LaBauve, Annette E.; Rinker, Torri E.; Noureddine, Achraf Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-32033-w	journal	September 2018
The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials Suder, Ellen; Furuyama, Wakako; Feldmann, Heinz Human Vaccines & Immunotherapeutics, Vol. 14, Issue 9 https://doi.org/10.1080/21645515.2018.1473698	journal	June 2018
Codelivery of CRISPR-Cas9 and chlorin e6 for spatially controlled tumor-specific gene editing with synergistic drug effects Deng, Shaohui; Li, Xiaoxia; Liu, Shuang Science Advances, Vol. 6, Issue 29 https://doi.org/10.1126/sciadv.abb4005	journal	July 2020
Protein Identification and Analysis Tools on the ExPASy Server Gasteiger, Elisabeth; Hoogland, Christine; Gattiker, Alexandre The Proteomics Protocols Handbook https://doi.org/10.1385/1-59259-890-0:571	book	January 2005
Overview, Control Strategies, and Lessons Learned in the CDC Response to the 2014–2016 Ebola Epidemic Bell, Beth P.; Damon, Inger K.; Jernigan, Daniel B. MMWR Supplements, Vol. 65, Issue 3 https://doi.org/10.15585/mmwr.su6503a2	journal	July 2016
Mesoporous Silica Nanoparticles for Protein Protection and Delivery Xu, Chun; Lei, Chang; Yu, Chengzhong Frontiers in Chemistry, Vol. 7 https://doi.org/10.3389/fchem.2019.00290	journal	May 2019
Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy Xiao, Qiaoqiao; Guo, Deyin; Chen, Shuliang Frontiers in Cellular and Infection Microbiology, Vol. 9 https://doi.org/10.3389/fcimb.2019.00069	journal	March 2019
The Application of CRISPR/Cas Systems for Antiviral Therapy Baddeley, Helen J. E.; Isalan, Mark Frontiers in Genome Editing, Vol. 3 https://doi.org/10.3389/fgeed.2021.745559	journal	October 2021
Viral Pandemics of the Last Four Decades: Pathophysiology, Health Impacts and Perspectives Roychoudhury, Shubhadeep; Das, Anandan; Sengupta, Pallav International Journal of Environmental Research and Public Health, Vol. 17, Issue 24 https://doi.org/10.3390/ijerph17249411	journal	December 2020
Ex Vivo Red Blood Cell Hemolysis Assay for the Evaluation of pH-responsive Endosomolytic Agents for Cytosolic Delivery of Biomacromolecular Drugs Evans, Brian C.; Nelson, Christopher E.; Yu, Shann S. Journal of Visualized Experiments, Issue 73 https://doi.org/10.3791/50166	journal	March 2013
A molecular view on the escape of lipoplexed DNA from the endosome Bruininks, Bart MH; Souza, Paulo CT; Ingolfsson, Helgi eLife, Vol. 9 https://doi.org/10.7554/eLife.52012	journal	April 2020

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