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Vol. 15 (2023)

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy

https://doi.org/10.1007/s40820-023-01153-y
Chun‑Jie Bao
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Jia‑Lun Duan
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Ying Xie
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Xin‑Ping Feng
School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China
Wei Cui
School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China
Song‑Yue Chen
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Pei‑Shan Li
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Yi‑Xuan Liu
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Jin‑Ling Wang
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Gui‑Ling Wang
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
Wan‑Liang Lu
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China

Corresponding Author: Wan‑Liang Lu

luwl@bjmu.edu.cn

Nano-Micro Letters, Vol. 15 (2023), Article Number: 197

Abstract

Gene therapy offers potentially transformative strategies for major human diseases. However, one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue. Here, we report a novel virus-like nanoparticle, the bioorthgonal engineered virus-like recombinant biosome (reBiosome), for efficient gene therapies of cancer and inflammatory diseases. The mutant virus-like biosome (mBiosome) is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site, and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry. The results show that the reBiosome exhibits reduced virus-like immunogenicity, prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci (like tumor and arthritic tissue). Furthermore, reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems, respectively. In conclusion, this study develops a universal, safe and efficient platform for gene therapies for cancer and inflammatory diseases.


Highlights:
1 A virus-like nanoparticle (reBiosome) was developed via site-specific codon mutation for displaying unnatural amino acid (Azi) on virus envelope protein at a rational site, followed by conjugating weak acid-responsive polyethylene glycol polymer on Azi via bioorthogonal chemistry.
2 The reBiosome exhibited reduced virus-like immunogenicity, prolonged blood circulation and enhanced delivery to weakly acidic disease foci.
3 The reBiosome enabled efficient delivery of gene editing and gene silencing system, demonstrating remarkable therapeutic efficacy in breast cancer and arthritis, respectively.

Keywords

Virus-like nanoparticle Site-specific codon mutation Recombinant biosome Bioorthogonal chemistry Gene therapy
Bao, Chun‑Jie, Jia‑Lun Duan, Ying Xie, Xin‑Ping Feng, Wei Cui, Song‑Yue Chen, Pei‑Shan Li, Yi‑Xuan Liu, Jin‑Ling Wang, Gui‑Ling Wang, and Wan‑Liang Lu. 2023. “Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy”. Nano-Micro Letters 15 (August):197. https://doi.org/10.1007/s40820-023-01153-y.
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References
  1. K.B. Kaufmann, H. Buning, A. Galy, A. Schambach, M. Grez, Gene therapy on the move. EMBO Mol. Med. 5(11), 1642–1661 (2013). https://doi.org/10.1002/emmm.201202287
  2. H. Yin, R.L. Kanasty, A.A. Eltoukhy, A.J. Vegas, J.R. Dorkin et al., Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15(8), 541–555 (2014). https://doi.org/10.1038/nrg3763
  3. J.T. Bulcha, Y. Wang, H. Ma, P.W.L. Tai, G. Gao, Viral vector platforms within the gene therapy landscape. Signal Transduct. Target Ther. 6(1), 53 (2021). https://doi.org/10.1038/s41392-021-00487-6
  4. J. Duan, C. Bao, Y. Xie, H. Guo, Y. Liu et al., Targeted core-shell nanops for precise ctcf gene insert in treatment of metastatic breast cancer. Bioact. Mater. 11, 1–14 (2022). https://doi.org/10.1016/j.bioactmat.2021.10.007
  5. D. Witzigmann, J.A. Kulkarni, J. Leung, S. Chen, P.R. Cullis et al., Lipid nanop technology for therapeutic gene regulation in the liver. Adv. Drug Deliv. Rev. 159, 344–363 (2020). https://doi.org/10.1016/j.addr.2020.06.026
  6. M.S. Sands, Aav-mediated liver-directed gene therapy. Methods Mol. Biol. 807, 141–157 (2011). https://doi.org/10.1007/978-1-61779-370-7_6
  7. S. Nooraei, H. Bahrulolum, Z.S. Hoseini, C. Katalani, A. Hajizade et al., Virus-like ps: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J. Nanobiotechnol. 19(1), 59 (2021). https://doi.org/10.1186/s12951-021-00806-7
  8. J.L. Mejia-Mendez, R. Vazquez-Duhalt, L.R. Hernandez, E. Sanchez-Arreola, H. Bach, Virus-like ps: fundamentals and biomedical applications. Int. J. Mol. Sci. 23(15), 8579 (2022). https://doi.org/10.3390/ijms23158579
  9. D. Stuart, P. Gouet, Viral envelope glycoproteins swing into action. Structure 3(7), 645–648 (1995). https://doi.org/10.1016/S0969-2126(01)00199-X
  10. P.C. Roberts, T. Kipperman, R.W. Compans, Vesicular stomatitis virus g protein acquires ph-independent fusion activity during transport in a polarized endometrial cell line. J. Virol. 73(12), 10447–10457 (1999). https://doi.org/10.1128/JVI.73.12.10447-10457.1999
  11. M. Bostina, H. Levy, D.J. Filman, J.M. Hogle, Poliovirus rna is released from the capsid near a twofold symmetry axis. J. Virol. 85(2), 776–783 (2011). https://doi.org/10.1128/jvi.00531-10
  12. J.R. Schnell, J.J. Chou, Structure and mechanism of the m2 proton channel of influenza a virus. Nature 451(7178), 591–595 (2008). https://doi.org/10.1038/nature06531
  13. Y. Barenholz, Doxil(r)–the first fda-approved nano-drug: Lessons learned. J. Control. Release 160(2), 117–134 (2012). https://doi.org/10.1016/j.jconrel.2012.03.020
  14. M.C. Pinder, N.K. Ibrahim, Nanop albumin-bound paclitaxel for treatment of metastatic breast cancer. Drugs Today 42(9), 599–604 (2006). https://doi.org/10.1358/dot.2006.42.9.1009902
  15. Z. Zhou, Y. Liu, X. Jiang, C. Zheng, W. Luo et al., Metformin modified chitosan as a multi-functional adjuvant to enhance cisplatin-based tumor chemotherapy efficacy. Int. J. Biol. Macromol. 224, 797–809 (2023). https://doi.org/10.1016/j.ijbiomac.2022.10.167
  16. Z. Zhou, Y. Liu, W. Song, X. Jiang, Z. Deng et al., Metabolic reprogramming mediated pd-l1 depression and hypoxia reversion to reactivate tumor therapy. J. Control. Release 352, 793–812 (2022). https://doi.org/10.1016/j.jconrel.2022.11.004
  17. S.A. Smith, L.I. Selby, A.P.R. Johnston, G.K. Such, The endosomal escape of nanops: toward more efficient cellular delivery. Bioconjug. Chem. 30(2), 263–272 (2019). https://doi.org/10.1021/acs.bioconjchem.8b00732
  18. Q. Zhang, G. Kuang, W. Li, J. Wang, H. Ren et al., Stimuli-responsive gene delivery nanocarriers for cancer therapy. Nano-Micro Lett. 15(1), 44 (2023). https://doi.org/10.1007/s40820-023-01018-4
  19. B. Schwarz, M. Uchida, T. Douglas, Biomedical and catalytic opportunities of virus-like ps in nanotechnology. Adv. Virus Res. 97, 1–60 (2017). https://doi.org/10.1016/bs.aivir.2016.09.002
  20. M.F. Bachmann, G.T. Jennings, Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat. Rev. Immunol. 10(11), 787–796 (2010). https://doi.org/10.1038/nri2868
  21. A. Gutierrez-Guerrero, F.L. Cosset, E. Verhoeyen, Lentiviral vector pseudotypes: precious tools to improve gene modification of hematopoietic cells for research and gene therapy. Viruses 12(9), 1016 (2020). https://doi.org/10.3390/v12091016
  22. M. Segel, B. Lash, J. Song, A. Ladha, C.C. Liu et al., Mammalian retrovirus-like protein peg10 packages its own mrna and can be pseudotyped for mrna delivery. Science 373(6557), 882–889 (2021). https://doi.org/10.1126/science.abg6155
  23. D. Finkelshtein, A. Werman, D. Novick, S. Barak, M. Rubinstein, Ldl receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc. Natl. Acad. Sci. USA 110(18), 7306–7311 (2013). https://doi.org/10.1073/pnas.1214441110
  24. J. Nikolic, L. Belot, H. Raux, P. Legrand, Y. Gaudin, Structural basis for the recognition of ldl-receptor family members by vsv glycoprotein. Nat. Commun. 9(1), 1029 (2018). https://doi.org/10.1038/s41467-018-03432-4
  25. H.K. Johannsdottir, R. Mancini, J. Kartenbeck, L. Amato, A. Helenius, Host cell factors and functions involved in vesicular stomatitis virus entry. J. Virol. 83(1), 440–453 (2009). https://doi.org/10.1128/JVI.01864-08
  26. S.S. Strickler, A.V. Gribenko, A.V. Gribenko, T.R. Keiffer, J. Tomlinson et al., Protein stability and surface electrostatics: a charged relationship. Biochemistry 45(9), 2761–2766 (2006). https://doi.org/10.1021/bi0600143
  27. H.X. Zhou, X. Pang, Electrostatic interactions in protein structure, folding, binding, and condensation. Chem. Rev. 118(4), 1691–1741 (2018). https://doi.org/10.1021/acs.chemrev.7b00305
  28. R. Alsallaq, H.X. Zhou, Electrostatic rate enhancement and transient complex of protein-protein association. Proteins 71(1), 320–335 (2008). https://doi.org/10.1002/prot.21679
  29. R. Alsallaq, H.X. Zhou, Prediction of protein-protein association rates from a transition-state theory. Structure 15(2), 215–224 (2007). https://doi.org/10.1016/j.str.2007.01.005
  30. L. Belot, M. Ouldali, S. Roche, P. Legrand, Y. Gaudin et al., Crystal structure of mokola virus glycoprotein in its post-fusion conformation. PLoS Pathog. 16(3), e1008383 (2020). https://doi.org/10.1371/journal.ppat.1008383
  31. S. Roche, F.A. Rey, Y. Gaudin, S. Bressanelli, Structure of the prefusion form of the vesicular stomatitis virus glycoprotein g. Science 315(5813), 843–848 (2007). https://doi.org/10.1126/science.1135710
  32. N.J. DePolo, J.D. Reed, P.L. Sheridan, K. Townsend, S.L. Sauter et al., Vsv-g pseudotyped lentiviral vector ps produced in human cells are inactivated by human serum. Mol. Ther. 2(3), 218–222 (2000). https://doi.org/10.1006/mthe.2000.0116
  33. V. Appay, S.L. Rowland-Jones, Rantes: a versatile and controversial chemokine. Trends Immunol. 22(2), 83–87 (2001). https://doi.org/10.1016/s1471-4906(00)01812-3
  34. B. Moser, I. Clark-Lewis, R. Zwahlen, M. Baggiolini, Neutrophil-activating properties of the melanoma growth-stimulatory activity. J. Exp. Med. 171(5), 1797–1802 (1990). https://doi.org/10.1084/jem.171.5.1797
  35. J.H. Dufour, M. Dziejman, M.T. Liu, J.H. Leung, T.E. Lane et al., Ifn-gamma-inducible protein 10 (IP-10; CXCl10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J. Immunol. 168(7), 3195–3204 (2002). https://doi.org/10.4049/jimmunol.168.7.3195
  36. M.W. Carr, S.J. Roth, E. Luther, S.S. Rose, T.A. Springer, Monocyte chemoattractant protein-1 acts as a t-lymphocyte chemoattractant. Proc. Natl. Acad. Sci. USA 91(9), 3652–3656 (1994). https://doi.org/10.1073/pnas.91.9.3652
  37. M.G. Katze, Y. He, M. Gale, Viruses and interferon: a fight for supremacy. Nat. Rev. Immunol. 2(9), 675–687 (2002). https://doi.org/10.1038/nri888
  38. M.H. Orzalli, A. Smith, K.A. Jurado, A. Iwasaki, J.A. Garlick et al., An antiviral branch of the il-1 signaling pathway restricts immune-evasive virus replication. Mol. Cell. 71(5), 825–840 (2018). https://doi.org/10.1016/j.molcel.2018.07.009
  39. J.M. Rojas, M. Avia, V. Martín, N. Sevilla, Il-10: A multifunctional cytokine in viral infections. J. Immunol. Res. 2017, 6104054 (2017). https://doi.org/10.1155/2017/6104054
  40. T. Komastu, D.D. Ireland, C.S. Reiss, Il-12 and viral infections. Cytokine Growth Factor Rev. 9(3–4), 277–285 (1998). https://doi.org/10.1016/s1359-6101(98)00017-3
  41. S.R. Paludan, S.C. Mogensen, Virus-cell interactions regulating induction of tumor necrosis factor alpha production in macrophages infected with herpes simplex virus. J. Virol. 75(21), 10170–10178 (2001). https://doi.org/10.1128/JVI.75.21.10170-10178.2001
  42. D.H. Barouch, S. Santra, K. Tenner-Racz, P. Racz, M.J. Kuroda et al., Potent Cd4+ T cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing GP120 and GM-CSF. J. Immunol. 168(2), 562–568 (2002). https://doi.org/10.4049/jimmunol.168.2.562
  43. J.S. Suk, Q. Xu, N. Kim, J. Hanes, L.M. Ensign, Pegylation as a strategy for improving nanop-based drug and gene delivery. Adv. Drug Deliv. Rev. 99(Pt A), 28–51 (2016). https://doi.org/10.1016/j.addr.2015.09.012
  44. J.C. Garcia-Canaveras, L. Chen, J.D. Rabinowitz, The tumor metabolic microenvironment: lessons from lactate. Cancer Res. 79(13), 3155–3162 (2019). https://doi.org/10.1158/0008-5472.Can-18-3726
  45. C. Bao, J. Duan, Y. Xie, Y. Liu, P. Li et al., A novel oncogenic enhancer of estrogen receptor-positive breast cancer. Mol. Ther. Nucleic Acids 29, 836–851 (2022). https://doi.org/10.1016/j.omtn.2022.08.029
  46. H. Matsuno, K. Yudoh, R. Katayama, F. Nakazawa, M. Uzuki et al., The role of tnf-alpha in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human ra/scid mouse chimera. Rheumatology 41(3), 329–337 (2002). https://doi.org/10.1093/rheumatology/41.3.329
  47. K.M. Pietrosimone, M. Jin, B. Poston, P. Liu, Collagen-induced arthritis: a model for murine autoimmune arthritis. Bio Protoc. 5(20), 1626 (2015). https://doi.org/10.21769/bioprotoc.1626
  48. D.D. Brand, K.A. Latham, E.F. Rosloniec, Collagen-induced arthritis. Nat. Protoc. 2(5), 1269–1275 (2007). https://doi.org/10.1038/nprot.2007.173
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