IJMMS_2024v14n3

International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 155-166 http://medscipublisher.com/index.php/ijmms 164 8 Concluding Remarks CRISPR/Cas9 technology has significantly advanced the field of xenotransplantation, particularly in the context of pig-to-human organ transplants. The ability to precisely edit the genome has allowed researchers to create genetically modified pigs that are less likely to trigger acute immunological reactions in human recipients. This has been achieved by targeting specific genes responsible for immune rejection and other incompatibilities. The technology has also been instrumental in studying the functions and mechanisms of various biological processes, thereby providing a deeper understanding of the genetic factors involved in xenotransplantation. Despite the remarkable progress, several challenges remain. One of the primary issues is the efficiency and specificity of CRISPR/Cas9-mediated gene editing. Off-target effects and incomplete gene edits can lead to unintended consequences, which are particularly concerning in a clinical setting. Additionally, the delivery methods for CRISPR/Cas9 components need to be optimized to ensure that the gene edits are made precisely and efficiently in the target tissues. Another significant challenge is the ethical and regulatory landscape surrounding the use of genetically modified organisms for medical purposes, which requires careful consideration and ongoing dialogue. The advancements in CRISPR/Cas9 technology hold immense promise for the future of xenotransplantation and organ transplantation. By overcoming the immunological barriers and improving the compatibility of pig organs for human use, CRISPR/Cas9 could potentially address the severe shortage of human organs available for transplantation. Furthermore, the technology's ability to make precise genetic modifications opens up new avenues for personalized medicine, where organs could be tailored to the genetic profile of individual patients, thereby reducing the risk of rejection and improving long-term outcomes. As research continues to address the existing challenges, the integration of CRISPR/Cas9 in clinical practice could revolutionize the field of organ transplantation, offering new hope to patients worldwide. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Blitz I., and Nakayama T., 2021, CRISPR-Cas9 Mutagenesis in xenopus tropicalis for phenotypic analyses in the F0 generation and beyond, Cold Spring Harbor protocols, 8: 106971. https://doi.org/10.1101/pdb.prot106971 PMid:34244352 Chen M., Mao A., Xu M., Weng Q., Mao J., and Ji J., 2019, CRISPR-Cas9 for cancer therapy: Opportunities and challenges, Cancer letters, 447: 48-55. https://doi.org/10.1016/j.canlet.2019.01.017 PMid:30684591 Cowan P., Hawthorne W., and Nottle M., 2019, Xenogeneic transplantation and tolerance in the era of CRISPR-Cas9. Current Opinion in Organ Transplantation, 24: 5-11. https://doi.org/10.1097/MOT.0000000000000589 PMid:30480643 Guo C., Ma X., Gao F., and Guo Y., 2023, Off-target effects in CRISPR/Cas9 gene editing, Frontiers in Bioengineering and Biotechnology, 11: 1143157. https://doi.org/10.3389/fbioe.2023.1143157 PMid:36970624 PMCid:PMC10034092 Hsu P., Lander E., and Zhang F., 2014, Development and applications of CRISPR-Cas9 for genome engineering, Cell, 157: 1262-1278. https://doi.org/10.1016/j.cell.2014.05.010 PMid:24906146 PMCid:PMC4343198 Hulton C., Costa E., Shah N., Quintanal-Villalonga A., Heller G., Stanchina E., Rudin C., and Poirier J., 2020, Direct genome editing of patient-derived xenografts using CRISPR-Cas9 enables rapid in vivo functional genomics, Nature cancer, 1: 359-369. https://doi.org/10.1038/s43018-020-0040-8 PMid:33345196 PMCid:PMC7745982 Jiang F., and Doudna J.A., 2017, CRISPR–Cas9 structures and mechanisms, Annual review of biophysics, 46: 505-529. https://doi.org/10.1146/annurev-biophys-062215-010822 PMid:28375731

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