Engineering Strategies And Therapeutic Applications Of In Vivo Anti-Tumor Gene Delivery Platforms
DOI:
https://doi.org/10.62051/mdt4x187Keywords:
Gene Therapy Vectors; AAV (Adeno-associated Virus); mRNA-Lipid Nanoparticles (LNPs); Oncolytic Viruses (OVs); Cancer Immunotherapy.Abstract
Gene therapy for cancer has received extensive attention in recent years. Adeno-associated virus (AAV), messenger RNA delivered by lipid nanoparticles (mRNA-LNP), and oncolytic viruses (OVs) are the three most actively studied delivery platforms. The three have different advantages in anti-tumor factor expression, immune activation, and targeting ability. Current research has made positive progress in animal models and preclinical experiments, but there are still obvious challenges in delivery efficiency, targeting control, and safety. This article systematically analyzes the engineering optimization strategies of the three types of gene therapy, including capsid modification and promoter regulation of AAV, lipid screening and surface engineering of mRNA-LNP, and targeted diffusion mechanism and immune enhancement design of OVs. The results show that these delivery platforms can achieve more efficient tumor targeting and therapeutic gene expression through engineering means. The study provides comprehensive theoretical support and technical reference for future cancer gene therapy, but problems such as off-target effects, immunogenicity, and clinical transformation efficiency still need to be solved. Future work can focus on the construction of individualized delivery platforms and multi-therapy synergistic strategies to achieve more precise, safe, and broad-spectrum tumor treatment effects.
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[1] Santiago-Ortiz, J. L., & Schaffer, D. V. Adeno-associated virus (AAV) vectors in cancer gene therapy. Journal of Controlled Release, 2016, 240: 287-301.
[2] Zong, Y., Lin, Y., Wei, T., & Cheng, Q. Lipid nanoparticle (LNP) enables mRNA delivery for cancer therapy. Advanced Materials, 2023, 35(51), 2303261.
[3] Apolonio, J. S., de Souza Gonçalves, V. L., Santos, M. L. C., Luz, M. S., Souza, J. V. S., Pinheiro, S. L. R., ... & de Melo, F. F. Oncolytic virus therapy in cancer: A current review. World journal of virology, 2021, 10(5): 229.
[4] Mahendra, G., Kumar, S., Isayeva, T., Mahasreshti, P. J., Curiel, D. T., Stockardt, C. R., ... & Ponnazhagan, S. Antiangiogenic cancer gene therapy by adeno-associated virus 2-mediated stable expression of the soluble FMS-like tyrosine kinase-1 receptor. Cancer gene therapy, 2005, 12(1): 26-34.
[5] Yu, D. L., Stegelmeier, A. A., Chow, N., Rghei, A. D., Matuszewska, K., Lawler, J., ... & Wootton, S. K.AAV-mediated expression of 3TSR inhibits tumor and metastatic lesion development and extends survival in a murine model of epithelial ovarian carcinoma. Cancer gene therapy, 2020, 27(5): 356-367.
[6] Zi-Bo, L. I., Zhao-Jun, Z. E. N. G., Qian, C. H. E. N., Sai-Qun, L. U. O., & Wei-Xin, H. U. Recombinant AAV-mediated HSVtk gene transfer with direct intratumoral injections and Tet-On regulation for implanted human breast cancer. BMC cancer, 2006, 6: 1-8.
[7] Chiu, T. L., Wang, M. J., & Su, C. C. The treatment of glioblastoma multiforme through activation of microglia and TRAIL induced by rAAV2-mediated IL-12 in a syngeneic rat model. Journal of biomedical science, 2012, 19: 1-15.
[8] Grifman, M., Trepel, M., Speece, P., Gilbert, L. B., Arap, W., Pasqualini, R., & Weitzman, M. D. Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. Molecular Therapy, 2001, 3(6): 964-975.
[9] Egeblad, M., & Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nature reviews cancer, 2002, 2(3): 161-174.
[10] Michelfelder, S., Kohlschütter, J., Skorupa, A., Pfennings, S., & Müller, O. Successful Expansion but Not Complete Restriction of Tropism of Adeno, 2009.
[11] Cai, W., Luo, T., Chen, X., Mao, L., & Wang, M. A combinatorial library of biodegradable lipid nanoparticles preferentially deliver mRNA into tumor cells to block mutant RAS signaling. Advanced Functional Materials, 2022, 32(41), 2204947.
[12] Maroun, J., Muñoz-Alía, M., Ammayappan, A., Schulze, A., Peng, K. W., & Russell, S. Designing and building oncolytic viruses. Future virology, 2017, 12(4): 193-213.
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