Animal Reproduction (AR)
https://animal-reproduction.org/article/doi/10.1590/1984-3143-AR2023-0089
Animal Reproduction (AR)
REVIEW ARTICLE

Gene editing in small and large animals for translational medicine: a review

Clésio Gomes Mariano Junior; Vanessa Cristina de Oliveira; Carlos Eduardo Ambrósio

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Abstract

The CRISPR/Cas9 system is a simpler and more versatile method compared to other engineered nucleases such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs), and since its discovery, the efficiency of CRISPR-based genome editing has increased to the point that multiple and different types of edits can be made simultaneously. These advances in gene editing have revolutionized biotechnology by enabling precise genome editing with greater simplicity and efficacy than ever before. This tool has been successfully applied to a wide range of animal species, including cattle, pigs, dogs, and other small animals. Engineered nucleases cut the genome at specific target positions, triggering the cell's mechanisms to repair the damage and introduce a mutation to a specific genomic site. This review discusses novel genome-based CRISPR/Cas9 editing tools, methods developed to improve efficiency and specificity, the use of gene-editing on animal models and translational medicine, and the main challenges and limitations of CRISPR-based gene-editing approaches.

Keywords

animal models, CRISPR, gene editing, translational medicine

References

Abdolahi S, Ghazvinian Z, Muhammadnejad S, Saleh M, Asadzadeh Aghdaei H, Baghaei K. Patient-derived xenograft (PDX) models, applications and challenges in cancer research. J Transl Med. 2022;20(1):206. http://dx.doi.org/10.1186/s12967-022-03405-8. PMid:35538576.

Adli M. The CRISPR tool kit for genome editing and beyond. Nat Commun. 2018;9(1):1911. http://dx.doi.org/10.1038/s41467-018-04252-2. PMid:29765029.

Aird WC. Discovery of the cardiovascular system: from Galen to William Harvey. J Thromb Haemost. 2011;9(Suppl 1):118-29. http://dx.doi.org/10.1111/j.1538-7836.2011.04312.x. PMid:21781247.

Albadri S, Del Bene F, Revenu C. Genome editing using CRISPR/Cas9-based knock-in approaches in zebrafish. Methods. 2017;121-122:77-85. http://dx.doi.org/10.1016/j.ymeth.2017.03.005. PMid:28300641.

Amoasii L, Hildyard JC, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, Harron R, Stathopoulou T, Massey C, Shelton JM, Bassel-Duby R, Piercy RJ, Olson EN. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science. 2018;362(6410):86-91. http://dx.doi.org/10.1126/science.aau1549. PMid:30166439.

Anzalone AV, Koblan LW, Liu DR. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol. 2020;38(7):824-44. http://dx.doi.org/10.1038/s41587-020-0561-9. PMid:32572269.

Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, Chen PJ, Wilson C, Newby JA, Raguram A, Liu DR. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149-57. http://dx.doi.org/10.1038/s41586-019-1711-4. PMid:31634902.

Baltzer WI, Calise DV, Levine JM, Shelton GD, Edwards JF, Steiner JM. Dystrophin-deficient muscular dystrophy in a weimaraner. J Am Anim Hosp Assoc. 2007;43(4):227-32. http://dx.doi.org/10.5326/0430227. PMid:17615404.

Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315(5819):1709-12. http://dx.doi.org/10.1126/science.1138140. PMid:17379808.

Bellipanni G, Cappello F, Scalia F, Conway de Macario E, Macario AJ, Giordano A. Zebrafish as a Model for the Study of Chaperonopathies. J Cell Physiol. 2016;231(10):2107-14. http://dx.doi.org/10.1002/jcp.25319. PMid:26812965.

Benhar I, London A, Schwartz M. The privileged immunity of immune privileged organs: the case of the eye. Front Immunol. 2012;3:296. http://dx.doi.org/10.3389/fimmu.2012.00296. PMid:23049533.

Bhardwaj A, Nain V. TALENs: an indispensable tool in the era of CRISPR: a mini review. J Genet Eng Biotechnol. 2021;19(1):125. http://dx.doi.org/10.1186/s43141-021-00225-z. PMid:34420096.

Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim Y-G, Chandrasegaran S. Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol. 2001;21(1):289-97. http://dx.doi.org/10.1128/MCB.21.1.289-297.2001. PMid:11113203.

Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 2009;326(5959):1509-12. http://dx.doi.org/10.1126/science.1178811. PMid:19933107.

Bolotin A, Quinquis B, Sorokin A, Ehrlich SD. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology (Reading). 2005;151(Pt 8):2551-61. http://dx.doi.org/10.1099/mic.0.28048-0. PMid:16079334.

Bulfield G, Siller WG, Wight PA, Moore KJ. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci USA. 1984;81(4):1189-92. http://dx.doi.org/10.1073/pnas.81.4.1189. PMid:6583703.

Camargo LSA, Saraiva NZ, Oliveira CS, Carmickle A, Lemos DR, Siqueira LGB, Denicol AC. Perspectives of gene editing for cattle farming in tropical and subtropical regions. Anim Reprod. 2023;19(4):e20220108. http://dx.doi.org/10.1590/1984-3143-ar2022-0108. PMid:36819485.

Carroll D. Focus: genome editing: genome editing: past, present, and future. Yale J Biol Med. 2017;90(4):653-9. PMid:29259529.

Castellani G, Croese T, Peralta Ramos JM, Schwartz M. Transforming the understanding of brain immunity. Science. 2023;380(6640):eabo7649. http://dx.doi.org/10.1126/science.abo7649. PMid:37023203.

Chamberlain JS, Metzger J, Reyes M, Townsend DW, Faulkner JA. Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma. FASEB J. 2007;21(9):2195-204. http://dx.doi.org/10.1096/fj.06-7353com. PMid:17360850.

Chapman VM, Miller DR, Armstrong D, Caskey CT. Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc Natl Acad Sci USA. 1989;86(4):1292-6. http://dx.doi.org/10.1073/pnas.86.4.1292. PMid:2919177.

Charlesworth CT, Deshpande PS, Dever DP, Camarena J, Lemgart VT, Cromer MK, Vakulskas CA, Collingwood MA, Zhang L, Bode NM, Behlke MA, Dejene B, Cieniewicz B, Romano R, Lesch BJ, Gomez-Ospina N, Mantri S, Pavel-Dinu M, Weinberg KI, Porteus MH. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat Med. 2019;25(2):249-54. http://dx.doi.org/10.1038/s41591-018-0326-x. PMid:30692695.

Chen PJ, Liu DR. Prime editing for precise and highly versatile genome manipulation. Nat Rev Genet. 2023;24(3):161-77. http://dx.doi.org/10.1038/s41576-022-00541-1. PMid:36344749.

Cho SW, Kim S, Kim Y, Kweon J, Kim HS, Bae S, Kim JS. Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res. 2014;24(1):132-41. http://dx.doi.org/10.1101/gr.162339.113. PMid:24253446.

Chung SH, Sin TN, Ngo T, Yiu G. CRISPR technology for ocular angiogenesis. Frontiers in Genome Editing. 2020;2:594984. http://dx.doi.org/10.3389/fgeed.2020.594984. PMid:34713223.

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819-23. http://dx.doi.org/10.1126/science.1231143. PMid:23287718.

Crudele JM, Chamberlain JS. Cas9 immunity creates challenges for CRISPR gene editing therapies. Nat Commun. 2018;9(1):3497. http://dx.doi.org/10.1038/s41467-018-05843-9. PMid:30158648.

Dominguez AA, Lim WA, Qi LS. Beyond editing: repurposing CRISPR–Cas9 for precision genome regulation and interrogation. Nat Rev Mol Cell Biol. 2016;17(1):5-15. http://dx.doi.org/10.1038/nrm.2015.2. PMid:26670017.

Ebrahimi V, Hashemi A. Challenges of in vitro genome editing with CRISPR/Cas9 and possible solutions: a review. Gene. 2020;753:144813. http://dx.doi.org/10.1016/j.gene.2020.144813. PMid:32470504.

Ericsson AC, Crim MJ, Franklin CL. A brief history of animal modeling. Mo Med. 2013;110(3):201-5. PMid:23829102.

Fan Z, Perisse IV, Cotton CU, Regouski M, Meng Q, Domb C, Van Wettere AJ, Wang Z, Harris A, White KL, Polejaeva IA. A sheep model of cystic fibrosis generated by CRISPR/Cas9 disruption of the CFTR gene. JCI Insight. 2018;3(19):e123529. http://dx.doi.org/10.1172/jci.insight.123529. PMid:30282831.

Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014;32(3):279-84. http://dx.doi.org/10.1038/nbt.2808. PMid:24463574.

Fujiwara S. Humanized mice: a brief overview on their diverse applications in biomedical research. J Cell Physiol. 2018;233(4):2889-901. http://dx.doi.org/10.1002/jcp.26022. PMid:28543438.

Gaj T, Gersbach CA, Barbas CF 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405. http://dx.doi.org/10.1016/j.tibtech.2013.04.004. PMid:23664777.

Gao X, Tsang JC, Gaba F, Wu D, Lu L, Liu P. Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers. Nucleic Acids Res. 2014;42(20):e155. http://dx.doi.org/10.1093/nar/gku836. PMid:25223790.

Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, Liu DR. Programmable base editing of A• T to G• C in genomic DNA without DNA cleavage. Nature. 2017;551(7681):464-71. http://dx.doi.org/10.1038/nature24644. PMid:29160308.

Georges M, Charlier C, Hayes B. Harnessing genomic information for livestock improvement. Nat Rev Genet. 2019;20(3):135-56. http://dx.doi.org/10.1038/s41576-018-0082-2. PMid:30514919.

Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell. 2013;154(2):442-51. http://dx.doi.org/10.1016/j.cell.2013.06.044. PMid:23849981.

Glass Z, Lee M, Li Y, Xu Q. Engineering the delivery system for CRISPR-based genome editing. Trends Biotechnol. 2018;36(2):173-85. http://dx.doi.org/10.1016/j.tibtech.2017.11.006. PMid:29305085.

Gore AV, Pillay LM, Venero Galanternik M, Weinstein BM. The zebrafish: a fintastic model for hematopoietic development and disease. Wiley Interdiscip Rev Dev Biol. 2018;7(3):e312. http://dx.doi.org/10.1002/wdev.312. PMid:29436122.

Griffith BP, Goerlich CE, Singh AK, Rothblatt M, Lau CL, Shah A, Lorber M, Grazioli A, Saharia KK, Hong SN, Joseph SM, Ayares D, Mohiuddin MM. Genetically modified porcine-to-human cardiac xenotransplantation. N Engl J Med. 2022;387(1):35-44. http://dx.doi.org/10.1056/NEJMoa2201422. PMid:35731912.

Harrison PT, Hart S. A beginner’s guide to gene editing. Exp Physiol. 2018;103(4):439-48. http://dx.doi.org/10.1113/EP086047. PMid:29282799.

Hay AN, Farrell K, Leeth CM, Lee K. Use of genome editing techniques to produce transgenic farm animals. In: Wu G, editor. Recent advances in animal nutrition and metabolism. Cham: Springer; 2022. p. 279-97. http://dx.doi.org/10.1007/978-3-030-85686-1_14.

Helfer-Hungerbuehler AK, Shah J, Meili T, Boenzli E, Li P, Hofmann-Lehmann R. Adeno-associated vector-delivered CRISPR/Sa Cas9 system reduces feline leukemia virus production in vitro. Viruses. 2021;13(8):1636. http://dx.doi.org/10.3390/v13081636. PMid:34452500.

Hirakawa MP, Krishnakumar R, Timlin JA, Carney JP, Butler KS. Gene editing and CRISPR in the clinic: current and future perspectives. Biosci Rep. 2020;40(4):BSR20200127. http://dx.doi.org/10.1042/BSR20200127. PMid:32207531.

Hoareau M, El Kholti N, Debret R, Lambert E. Zebrafish as a model to study vascular elastic fibers and associated pathologies. Int J Mol Sci. 2022;23(4):2102. http://dx.doi.org/10.3390/ijms23042102. PMid:35216218.

Humphrey SE, Kasinski AL. RNA-guided CRISPR-Cas technologies for genome-scale investigation of disease processes. J Hematol Oncol. 2015;8(1):31. http://dx.doi.org/10.1186/s13045-015-0127-3. PMid:25888285.

Ikeda M, Matsuyama S, Akagi S, Ohkoshi K, Nakamura S, Minabe S, Kimura K, Hosoe M. Correction of a disease mutation using CRISPR/Cas9-assisted genome editing in Japanese black cattle. Sci Rep. 2017;7(1):17827. http://dx.doi.org/10.1038/s41598-017-17968-w. PMid:29259316.

Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987;169(12):5429-33. http://dx.doi.org/10.1128/jb.169.12.5429-5433.1987. PMid:3316184.

Jansen R, Embden JDV, Gaastra W, Schouls LM. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 2002;43(6):1565-75. http://dx.doi.org/10.1046/j.1365-2958.2002.02839.x. PMid:11952905.

Jiang F, Doudna JA. CRISPR–Cas9 structures and mechanisms. Annu Rev Biophys. 2017;46(1):505-29. http://dx.doi.org/10.1146/annurev-biophys-062215-010822. PMid:28375731.

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-21. http://dx.doi.org/10.1126/science.1225829. PMid:22745249.

Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49-55. http://dx.doi.org/10.1038/nrm3486. PMid:23169466.

Kalds P, Gao Y, Zhou S, Cai B, Huang X, Wang X, Chen Y. Redesigning small ruminant genomes with CRISPR toolkit: overview and perspectives. Theriogenology. 2020;147:25-33. http://dx.doi.org/10.1016/j.theriogenology.2020.02.015. PMid:32086048.

Kalds P, Zhou S, Cai B, Liu J, Wang Y, Petersen B, Sonstegard T, Wang X, Chen Y. Sheep and goat genome engineering: from random transgenesis to the CRISPR era. Front Genet. 2019;10:750. http://dx.doi.org/10.3389/fgene.2019.00750. PMid:31552084.

Kalueff AV, Stewart AM, Gerlai R. Zebrafish as an emerging model for studying complex brain disorders. Trends Pharmacol Sci. 2014;35(2):63-75. http://dx.doi.org/10.1016/j.tips.2013.12.002. PMid:24412421.

Kanellopoulos-Langevin C, Caucheteux SM, Verbeke P, Ojcius DM. Tolerance of the fetus by the maternal immune system: role of inflammatory mediators at the feto-maternal interface. Reprod Biol Endocrinol. 2003;1(1):121. http://dx.doi.org/10.1186/1477-7827-1-121. PMid:14651750.

Katoch S, Patial V. Zebrafish: an emerging model system to study liver diseases and related drug discovery. J Appl Toxicol. 2021;41(1):33-51. http://dx.doi.org/10.1002/jat.4031. PMid:32656821.

Key J, Maletzko A, Kohli A, Gispert S, Torres-Odio S, Wittig I, Heidler J, Bárcena C, López-Otín C, Lei Y, West AP, Münch C, Auburger G. Loss of mitochondrial ClpP, Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease. Neurogenetics. 2020;21(3):187-203. http://dx.doi.org/10.1007/s10048-020-00609-2. PMid:32342250.

Khan SH. Genome-editing technologies: concept, pros, and cons of various genome-editing techniques and bioethical concerns for clinical application. Mol Ther Nucleic Acids. 2019;16:326-34. http://dx.doi.org/10.1016/j.omtn.2019.02.027. PMid:30965277.

Kim SC, Mathews DV, Breeden CP, Higginbotham LB, Ladowski J, Martens G, Stephenson A, Farris AB, Strobert EA, Jenkins J, Walters EM, Larsen CP, Tector M, Tector AJ, Adams AB. Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion. Am J Transplant. 2019;19(8):2174-85. http://dx.doi.org/10.1111/ajt.15329. PMid:30821922.

Kim YB, Komor AC, Levy JM, Packer MS, Zhao KT, Liu DR. Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat Biotechnol. 2017;35(4):371-6. http://dx.doi.org/10.1038/nbt.3803. PMid:28191901.

Klymiuk N, Blutke A, Graf A, Krause S, Burkhardt K, Wuensch A, Krebs S, Kessler B, Zakhartchenko V, Kurome M, Kemter E, Nagashima H, Schoser B, Herbach N, Blum H, Wanke R, Aartsma-Rus A, Thirion C, Lochmüller H, Walter MC, Wolf E. Dystrophin deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle. Hum Mol Genet. 2013;22(21):4368-82. http://dx.doi.org/10.1093/hmg/ddt287. PMid:23784375.

Knott GJ, Doudna JA. CRISPR-Cas guides the future of genetic engineering. Science. 2018;361(6405):866-9. http://dx.doi.org/10.1126/science.aat5011. PMid:30166482.

Koblan LW, Doman JL, Wilson C, Levy JM, Tay T, Newby GA, Maianti JP, Raguram A, Liu DR. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat Biotechnol. 2018;36(9):843-6. http://dx.doi.org/10.1038/nbt.4172. PMid:29813047.

Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533(7603):420-4. http://dx.doi.org/10.1038/nature17946. PMid:27096365.

Komor AC, Zhao KT, Packer MS, Gaudelli NM, Waterbury AL, Koblan LW, Kim YB, Badran AH, Liu DR. Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci Adv. 2017;3(8):eaao4774. http://dx.doi.org/10.1126/sciadv.aao4774. PMid:28875174.

Kotagama OW, Jayasinghe CD, Abeysinghe T. Era of genomic medicine: a narrative review on CRISPR technology as a potential therapeutic tool for human diseases. BioMed Res Int. 2019;2019:1369682. http://dx.doi.org/10.1155/2019/1369682. PMid:31687377.

Kreitz J, Friedrich MJ, Guru A, Lash B, Saito M, Macrae RK, Zhang F. Programmable protein delivery with a bacterial contractile injection system. Nature. 2023;616(7956):357-64. http://dx.doi.org/10.1038/s41586-023-05870-7. PMid:36991127.

Lamas-Toranzo I, Galiano-Cogolludo B, Cornudella-Ardiaca F, Cobos-Figueroa J, Ousinde O, Bermejo-Alvarez P. Strategies to reduce genetic mosaicism following CRISPR-mediated genome edition in bovine embryos. Sci Rep. 2019;9(1):14900. http://dx.doi.org/10.1038/s41598-019-51366-8. PMid:31624292.

Längin M, Mayr T, Reichart B, Michel S, Buchholz S, Guethoff S, Dashkevich A, Baehr A, Egerer S, Bauer A, Mihalj M, Panelli A, Issl L, Ying J, Fresch AK, Buttgereit I, Mokelke M, Radan J, Werner F, Lutzmann I, Steen S, Sjöberg T, Paskevicius A, Qiuming L, Sfriso R, Rieben R, Dahlhoff M, Kessler B, Kemter E, Kurome M, Zakhartchenko V, Klett K, Hinkel R, Kupatt C, Falkenau A, Reu S, Ellgass R, Herzog R, Binder U, Wich G, Skerra A, Ayares D, Kind A, Schönmann U, Kaup F-J, Hagl C, Wolf E, Klymiuk N, Brenner P, Abicht JM. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature. 2018;564(7736):430-3. http://dx.doi.org/10.1038/s41586-018-0765-z. PMid:30518863.

Lawhorn IE, Ferreira JP, Wang CL. Evaluation of sgRNA target sites for CRISPR-mediated repression of TP53. PLoS One. 2014;9(11):e113232. http://dx.doi.org/10.1371/journal.pone.0113232. PMid:25398078.

Lee K, Uh K, Farrell K. Current progress of genome editing in livestock. Theriogenology. 2020;150:229-35. http://dx.doi.org/10.1016/j.theriogenology.2020.01.036. PMid:32000993.

Lin Y, Li J, Li C, Tu Z, Li S, Li XJ, Yan S. Application of CRISPR/Cas9 system in establishing large animal models. Front Cell Dev Biol. 2022;10:919155. http://dx.doi.org/10.3389/fcell.2022.919155. PMid:35656550.

Lino CA, Harper JC, Carney JP, Timlin JA. Delivering CRISPR: a review of the challenges and approaches. Drug Deliv. 2018;25(1):1234-57. http://dx.doi.org/10.1080/10717544.2018.1474964. PMid:29801422.

Liu B, Dong X, Cheng H, Zheng C, Chen Z, Rodríguez TC, Liang SQ, Xue W, Sontheimer EJ. A split prime editor with untethered reverse transcriptase and circular RNA template. Nat Biotechnol. 2022;40(9):1388-93. http://dx.doi.org/10.1038/s41587-022-01255-9. PMid:35379962.

Liu Z, Chen S, Shan H, Jia Y, Chen M, Song Y, Lai L, Li Z. Efficient base editing with high precision in rabbits using YFE-BE4max. Cell Death Dis. 2020;11(1):36. http://dx.doi.org/10.1038/s41419-020-2244-3. PMid:31959743.

Lobanovska M, Pilla G. Penicillin’s discovery and antibiotic resistance: lessons for the future? Yale J Biol Med. 2017;90(1):135-45. PMid:28356901.

Ma D, Hirose T, Lassiter G, Sasaki H, Rosales I, Coe TM, Rickert CG, Matheson R, Colvin RB, Qin W, Kan Y, Layer JV, Paragas VB, Stiede K, Hall KC, Youd ME, Queiroz LM, Westlin WF, Curtis M, Yang L, Markmann JF, Kawai T. Kidney transplantation from triple‐knockout pigs expressing multiple human proteins in cynomolgus macaques. Am J Transplant. 2022;22(1):46-57. http://dx.doi.org/10.1111/ajt.16780. PMid:34331749.

Marraffini LA. CRISPR-Cas immunity in prokaryotes. Nature. 2015;526(7571):55-61. http://dx.doi.org/10.1038/nature15386. PMid:26432244.

Maynard LH, Humbert O, Peterson CW, Kiem HP. Genome editing in large animal models. Mol Ther. 2021;29(11):3140-52. http://dx.doi.org/10.1016/j.ymthe.2021.09.026. PMid:34601132.

McFarlane GR, Salvesen HA, Sternberg A, Lillico SG. On-farm livestock genome editing using cutting edge reproductive technologies. Front Sustain Food Syst. 2019;3:106. http://dx.doi.org/10.3389/fsufs.2019.00106.

McMahon MA, Rahdar M, Porteus M. Gene editing: not just for translation anymore. Nat Methods. 2011;9(1):28-31. http://dx.doi.org/10.1038/nmeth.1811. PMid:22205513.

Mehravar M, Shirazi A, Nazari M, Banan M. Mosaicism in CRISPR/Cas9-mediated genome editing. Dev Biol. 2019;445(2):156-62. http://dx.doi.org/10.1016/j.ydbio.2018.10.008. PMid:30359560.

Mei Y, Wang Y, Chen H, Sun ZS, Ju X-D. Recent progress in CRISPR/Cas9 technology. J Genet Genomics. 2016;43(2):63-75. http://dx.doi.org/10.1016/j.jgg.2016.01.001. PMid:26924689.

Menchaca A, Santos-Neto P, Mulet A, Crispo M. CRISPR in livestock: from editing to printing. Theriogenology. 2020;150:247-54. http://dx.doi.org/10.1016/j.theriogenology.2020.01.063. PMid:32088034.

Mendell JR, Lloyd-Puryear M. Report of MDA muscle disease symposium on newborn screening for Duchenne muscular dystrophy. Muscle Nerve. 2013;48(1):21-6. http://dx.doi.org/10.1002/mus.23810. PMid:23716304.

Mettelman RC, O’Brien A, Whittaker GR, Baker SC. Generating and evaluating type I interferon receptor-deficient and feline TMPRSS2-expressing cells for propagating serotype I feline infectious peritonitis virus. Virology. 2019;537:226-36. http://dx.doi.org/10.1016/j.virol.2019.08.030. PMid:31539770.

Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V. The Pig: a Model for Human Infectious Diseases. Trends Microbiol. 2012;20(1):50-7. http://dx.doi.org/10.1016/j.tim.2011.11.002. PMid:22153753.

Mohiuddin MM, Goerlich CE, Singh AK, Zhang T, Tatarov I, Lewis B, Sentz F, Hershfeld A, Braileanu G, Odonkor P, Strauss E, Williams B, Burke A, Hittman J, Bhutta A, Tabatabai A, Gupta A, Vaught T, Sorrells L, Kuravi K, Dandro A, Eyestone W, Kaczorowski DJ, Ayares D, Griffith BP. Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months. Xenotransplantation. 2022;29(3):e12744. http://dx.doi.org/10.1111/xen.12744. PMid:35357044.

Mohiuddin MM, Singh AK, Corcoran PC, Thomas ML 3rd, Clark T, Lewis BG, Hoyt RF, Eckhaus M, Pierson Iii RN, Belli AJ, Wolf E, Klymiuk N, Phelps C, Reimann KA, Ayares D, Horvath KA. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO. hCD46. hTBM pig-to-primate cardiac xenograft. Nat Commun. 2016;7(1):11138. http://dx.doi.org/10.1038/ncomms11138. PMid:27045379.

Mojica FJ, Díez-Villaseñor C, Soria E, Juez G. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, bacteria and mitochondria. Mol Microbiol. 2000;36(1):244-6. http://dx.doi.org/10.1046/j.1365-2958.2000.01838.x. PMid:10760181.

Mojica FJM, Díez-Villaseñor C, García-Martínez J, Soria E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol. 2005;60(2):174-82. http://dx.doi.org/10.1007/s00239-004-0046-3. PMid:15791728.

Montgomery RA, Stern JM, Lonze BE, Tatapudi VS, Mangiola M, Wu M, Weldon E, Lawson N, Deterville C, Dieter RA, Sullivan B, Boulton G, Parent B, Piper G, Sommer P, Cawthon S, Duggan E, Ayares D, Dandro A, Fazio-Kroll A, Kokkinaki M, Burdorf L, Lorber M, Boeke JD, Pass H, Keating B, Griesemer A, Ali NM, Mehta SA, Stewart ZA. Results of two cases of pig-to-human kidney xenotransplantation. N Engl J Med. 2022;386(20):1889-98. http://dx.doi.org/10.1056/NEJMoa2120238. PMid:35584156.

Mout R, Ray M, Lee YW, Scaletti F, Rotello VM. In vivo delivery of CRISPR/Cas9 for therapeutic gene editing: progress and challenges. Bioconjug Chem. 2017;28(4):880-4. http://dx.doi.org/10.1021/acs.bioconjchem.7b00057. PMid:28263568.

Navarro-Serna S, Hachem A, Canha-Gouveia A, Hanbashi A, Garrappa G, Lopes JS, París-Oller E, Sarrías-Gil L, Flores-Flores C, Bassett A, Sánchez R, Bermejo-Álvarez P, Matás C, Romar R, Parrington J, Gadea J. Generation of nonmosaic, two-pore channel 2 biallelic knockout pigs in one generation by CRISPR-Cas9 microinjection before oocyte insemination. CRISPR J. 2021;4(1):132-46. http://dx.doi.org/10.1089/crispr.2020.0078. PMid:33616447.

Navarro-Serna S, Vilarino M, Park I, Gadea J, Ross PJ. Livestock gene editing by one-step embryo manipulation. J Equine Vet Sci. 2020;89:103025. http://dx.doi.org/10.1016/j.jevs.2020.103025. PMid:32563448.

Ni W, Qiao J, Hu S, Zhao X, Regouski M, Yang M, Polejaeva IA, Chen C. Efficient gene knockout in goats using CRISPR/Cas9 system. PLoS One. 2014;9(9):e106718. http://dx.doi.org/10.1371/journal.pone.0106718. PMid:25188313.

Oliveira VC, Gomes Mariano C Jr, Belizário JE, Krieger JE, Fernandes Bressan F, Roballo KCS, Fantinato-Neto P, Meirelles FV, Chiaratti MR, Concordet JP, Ambrósio CE. Characterization of post-edited cells modified in the TFAM gene by CRISPR/Cas9 technology in the bovine model. PLoS One. 2020;15(7):e0235856. http://dx.doi.org/10.1371/journal.pone.0235856. PMid:32649732.

Oliveira VC, Moreira GSA, Bressan FF, Gomes Mariano C Jr, Roballo KCS, Charpentier M, Concordet JP, Ambrósio CE. Edition of TFAM gene by CRISPR/Cas9 technology in bovine model. PLoS One. 2019;14(3):e0213376. http://dx.doi.org/10.1371/journal.pone.0213376. PMid:30845180.

Outtandy P, Russell C, Kleta R, Bockenhauer D. Zebrafish as a model for kidney function and disease. Pediatr Nephrol. 2019;34(5):751-62. http://dx.doi.org/10.1007/s00467-018-3921-7. PMid:29502161.

Perisse IV, Fan Z, Singina GN, White KL, Polejaeva IA. Improvements in gene editing technology boost its applications in livestock. Front Genet. 2021;11:614688. http://dx.doi.org/10.3389/fgene.2020.614688. PMid:33603767.

Pineda M, Lear A, Collins JP, Kiani S. Safe CRISPR: challenges and possible solutions. Trends Biotechnol. 2019;37(4):389-401. http://dx.doi.org/10.1016/j.tibtech.2018.09.010. PMid:30352704.

Polejaeva IA, Campbell KHS. New advances in somatic cell nuclear transfer: application in transgenesis. Theriogenology. 2000;53(1):117-26. http://dx.doi.org/10.1016/S0093-691X(99)00245-9. PMid:10735067.

Polejaeva IA, Rutigliano HM, Wells KD. Livestock in biomedical research: history, current status and future prospective. Reprod Fertil Dev. 2016;28(1-2):112-24. http://dx.doi.org/10.1071/RD15343. PMid:27062879.

Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell. 2013;152(5):1173-83. http://dx.doi.org/10.1016/j.cell.2013.02.022. PMid:23452860.

Qomi SB, Asghari A, Mojarrad M. An overview of the CRISPR-based genomic-and epigenome-editing system: function, applications, and challenges. Adv Biomed Res. 2019;8(1):49. http://dx.doi.org/10.4103/abr.abr_41_19. PMid:31516887.

Ramakrishnan C, Maier S, Walker RA, Rehrauer H, Joekel DE, Winiger RR, Basso WU, Grigg ME, Hehl AB, Deplazes P, Smith NC. An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats. Sci Rep. 2019;9(1):1474. http://dx.doi.org/10.1038/s41598-018-37671-8. PMid:30728393.

Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520(7546):186-91. PMid:25830891.

Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 2013;154(6):1380-9. http://dx.doi.org/10.1016/j.cell.2013.08.021. PMid:23992846.

Rasul MF, Hussen BM, Salihi A, Ismael BS, Jalal PJ, Zanichelli A, Jamali E, Baniahmad A, Ghafouri-Fard S, Basiri A, Taheri M. Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy. Mol Cancer. 2022;21(1):64. http://dx.doi.org/10.1186/s12943-021-01487-4. PMid:35241090.

Rees HA, Liu DR. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet. 2018;19(12):770-88. http://dx.doi.org/10.1038/s41576-018-0059-1. PMid:30323312.

Reynolds LP, Ireland JJ, Caton JS, Bauman DE, Davis TA. Commentary on domestic animals in agricultural and biomedical research: an endangered enterprise. J Nutr. 2009;139(3):427-8. http://dx.doi.org/10.3945/jn.108.103564. PMid:19158219.

Robinson NB, Krieger K, Khan FM, Huffman W, Chang M, Naik A, Yongle R, Hameed I, Krieger K, Girardi LN, Gaudino M. The current state of animal models in research: a review. Int J Surg. 2019;72:9-13. http://dx.doi.org/10.1016/j.ijsu.2019.10.015. PMid:31627013.

Roth JA, Tuggle CK. Livestock models in translational medicine. ILAR J. 2015;56(1):1-6. http://dx.doi.org/10.1093/ilar/ilv011. PMid:25991694.

Roura E, Koopmans S-J, Lallès J-P, Le Huerou-Luron I, de Jager N, Schuurman T, Val-Laillet D. Critical Review Evaluating the Pig as a Model for Human Nutritional Physiology. Nutr Res Rev. 2016;29(1):60-90. http://dx.doi.org/10.1017/S0954422416000020. PMid:27176552.

Ryczek N, Hryhorowicz M, Zeyland J, Lipiński D, Słomski R. CRISPR/Cas technology in pig-to-human xenotransplantation research. Int J Mol Sci. 2021;22(6):3196. http://dx.doi.org/10.3390/ijms22063196. PMid:33801123.

Saito M, Xu P, Faure G, Maguire S, Kannan S, Altae-Tran H, Vo S, Desimone AA, Macrae RK, Zhang F. Fanzor is a eukaryotic programmable RNA-guided endonuclease. Nature. 2023;620(7974):660-8. http://dx.doi.org/10.1038/s41586-023-06356-2. PMid:37380027.

Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014;32(4):347-55. http://dx.doi.org/10.1038/nbt.2842. PMid:24584096.

Sharp NJH, Kornegay JN, Van Camp SD, Herbstreith MH, Secore SL, Kettle S, Hung W-Y, Constantinou CD, Dykstra MJ, Roses AD, Bartlett RJ. An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. Genomics. 1992;13(1):115-21. http://dx.doi.org/10.1016/0888-7543(92)90210-J. PMid:1577476.

Shen B, Zhang W, Zhang J, Zhou J, Wang J, Chen L, Wang L, Hodgkins A, Iyer V, Huang X, Skarnes WC. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat Methods. 2014;11(4):399-402. http://dx.doi.org/10.1038/nmeth.2857. PMid:24584192.

Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science. 1989;244(4912):1578-80. http://dx.doi.org/10.1126/science.2662404. PMid:2662404.

Silverman JL, Smith DG, Rizzo SJ, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley JN. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med. 2012;4(131):131ra51. http://dx.doi.org/10.1126/scitranslmed.3003501. PMid:22539775.

Smith BF, Yue YP, Woods PR, Kornegay JN, Shin J-H, Williams RR, Duan DS. An intronic LINE-1 element insertion in the dystrophin gene aborts dystrophin expression and results in Duchenne-like muscular dystrophy in the corgi breed. Lab Invest. 2011;91(2):216-31. http://dx.doi.org/10.1038/labinvest.2010.146. PMid:20714321.

Stoian A, Rowland RR, Petrovan V, Sheahan M, Samuel MS, Whitworth KM, Wells KD, Zhang J, Beaton B, Cigan M, Prather RS. The use of cells from ANPEP knockout pigs to evaluate the role of aminopeptidase N (APN) as a receptor for porcine deltacoronavirus (PDCoV). Virology. 2020;541:136-40. http://dx.doi.org/10.1016/j.virol.2019.12.007. PMid:32056711.

Sui T, Lau YS, Liu D, Liu T, Xu L, Gao Y, Lai L, Li J, Han R. A novel rabbit model of Duchenne muscular dystrophy generated by CRISPR/Cas9. Dis Model Mech. 2018;11(6):dmm032201. http://dx.doi.org/10.1242/dmm.032201. PMid:29871865.

Sykes M, Sachs DH. Progress in xenotransplantation: overcoming immune barriers. Nat Rev Nephrol. 2022;18(12):745-61. http://dx.doi.org/10.1038/s41581-022-00624-6. PMid:36198911.

Tanihara F, Hirata M, Nguyen NT, Le QA, Wittayarat M, Fahrudin M, Hirano T, Otoi T. Generation of CD163-edited pig via electroporation of the CRISPR/Cas9 system into porcine in vitro-fertilized zygotes. Anim Biotechnol. 2021;32(2):147-54. http://dx.doi.org/10.1080/10495398.2019.1668801. PMid:31558095.

Tay LS, Palmer N, Panwala R, Chew WL, Mali P. Translating CRISPR-Cas therapeutics: approaches and challenges. CRISPR J. 2020;3(4):253-75. http://dx.doi.org/10.1089/crispr.2020.0025. PMid:32833535.

Taylor TH, Gitlin SA, Patrick JL, Crain JL, Wilson JM, Griffin DK. The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans. Hum Reprod Update. 2014;20(4):571-81. http://dx.doi.org/10.1093/humupd/dmu016. PMid:24667481.

Thakore PI, Gersbach CA. Design, assembly, and characterization of tale-based transcriptional activators and repressors. Methods Mol Biol. 2016;1338:71-88. http://dx.doi.org/10.1007/978-1-4939-2932-0_7. PMid:26443215.

Tomita A, Sasanuma H, Owa T, Nakazawa Y, Shimada M, Fukuoka T, Ogi T, Nakada S. Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells. Nat Commun. 2023;14(1):5607. http://dx.doi.org/10.1038/s41467-023-41048-5. PMid:37714828.

Tucker EJ, Rius R, Jaillard S, Bell K, Lamont PJ, Travessa A, Dupont J, Sampaio L, Dulon J, Vuillaumier-Barrot S, Whalen S, Isapof A, Stojkovic T, Quijano-Roy S, Robevska G, van den Bergen J, Hanna C, Simpson A, Ayers K, Thorburn DR, Christodoulou J, Touraine P, Sinclair AH. Genomic sequencing highlights the diverse molecular causes of Perrault syndrome: a peroxisomal disorder (PEX6), metabolic disorders (CLPP, GGPS1), and mtDNA maintenance/translation disorders (LARS2, TFAM). Hum Genet. 2020;139(10):1325-43. http://dx.doi.org/10.1007/s00439-020-02176-w. PMid:32399598.

Walmsley GL, Arechavala-Gomeza V, Fernandez-Fuente M, Burke MM, Nagel N, Holder A, Stanley R, Chandler K, Marks SL, Muntoni F, Shelton GD, Piercy RJ. A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient cavalier king charles spaniels is amenable to exon 51 skipping. PLoS One. 2010;5(1):e8647. http://dx.doi.org/10.1371/journal.pone.0008647. PMid:20072625.

Wang JY, Doudna JA. CRISPR technology: a decade of genome editing is only the beginning. Science. 2023;379(6629):eadd8643. http://dx.doi.org/10.1126/science.add8643. PMid:36656942.

Wang X, Copmans D, Witte PA. Using zebrafish as a disease model to study fibrotic disease. Int J Mol Sci. 2021;22(12):6404. http://dx.doi.org/10.3390/ijms22126404. PMid:34203824.

Whitworth KM, Lee K, Benne JA, Beaton BP, Spate LD, Murphy SL, Samuel MS, Mao J, O’Gorman C, Walters EM, Murphy CN, Driver J, Mileham A, McLaren D, Wells KD, Prather RS. Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod. 2014;91(3):78. http://dx.doi.org/10.1095/biolreprod.114.121723. PMid:25100712.

Whitworth KM, Rowland RR, Petrovan V, Sheahan M, Cino-Ozuna AG, Fang Y, Hesse R, Mileham A, Samuel MS, Wells KD, Prather RS. Resistance to coronavirus infection in aminopeptidase N-deficient pigs. Transgenic Res. 2019;28(1):21-32. http://dx.doi.org/10.1007/s11248-018-0100-3. PMid:30315482.

Whitworth KM, Rowland RRR, Ewen CL, Trible BR, Kerrigan MA, Cino-Ozuna AG, Samuel MS, Lightner JE, McLaren DG, Mileham AJ, Wells KD, Prather RS. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nat Biotechnol. 2016;34(1):20-2. http://dx.doi.org/10.1038/nbt.3434. PMid:26641533.

Wilmut I, Schnieke AE, Mcwhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385(6619):810-3. http://dx.doi.org/10.1038/385810a0. PMid:9039911.

Wu J, Platero-Luengo A, Sakurai M, Sugawara A, Gil MA, Yamauchi T, Suzuki K, Bogliotti YS, Cuello C, Morales Valencia M, Okumura D, Luo J, Vilariño M, Parrilla I, Soto DA, Martinez CA, Hishida T, Sánchez-Bautista S, Martinez-Martinez ML, Wang H, Nohalez A, Aizawa E, Martinez-Redondo P, Ocampo A, Reddy P, Roca J, Maga EA, Esteban CR, Berggren WT, Nuñez Delicado E, Lajara J, Guillen I, Guillen P, Campistol JM, Martinez EA, Ross PJ, Izpisua Belmonte JC. Interspecies chimerism with mammalian pluripotent stem cells. Cell. 2017;168(3):473-86.e15. http://dx.doi.org/10.1016/j.cell.2016.12.036. PMid:28129541.

Xi J, Zheng W, Chen M, Zou Q, Tang C, Zhou X. Genetically engineered pigs for xenotransplantation: hopes and challenges. Front Cell Dev Biol. 2023;10:1093534. http://dx.doi.org/10.3389/fcell.2022.1093534. PMid:36712969.

Xie J, Ge W, Li N, Liu Q, Chen F, Yang X, Huang X, Ouyang Z, Zhang Q, Zhao Y, Liu Z, Gou S, Wu H, Lai C, Fan N, Jin Q, Shi H, Liang Y, Lan T, Quan L, Li X, Wang K, Lai L. Efficient base editing for multiple genes and loci in pigs using base editors. Nat Commun. 2019;10(1):2852. http://dx.doi.org/10.1038/s41467-019-10421-8. PMid:31253764.

Xu K, Zhou Y, Mu Y, Liu Z, Hou S, Xiong Y, Fang L, Ge C, Wei Y, Zhang X, Xu C, Che J, Fan Z, Xiang G, Guo J, Shang H, Li H, Xiao S, Li J, Li K. CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance. eLife. 2020;9:e57132. http://dx.doi.org/10.7554/eLife.57132. PMid:32876563.

Yan S, Tu Z, Liu Z, Fan N, Yang H, Yang S, Yang W, Zhao Y, Ouyang Z, Lai C, Yang H, Li L, Liu Q, Shi H, Xu G, Zhao H, Wei H, Pei Z, Li S, Lai L, Li XJ. A huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington’s disease. Cell. 2018;173(4):989-1002.e13. http://dx.doi.org/10.1016/j.cell.2018.03.005. PMid:29606351.

Yang H, Zhang J, Zhang X, Shi J, Pan Y, Zhou R, Li G, Li Z, Cai G, Wu Z. CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive and respiratory syndrome virus. Antiviral Res. 2018;151:63-70. http://dx.doi.org/10.1016/j.antiviral.2018.01.004. PMid:29337166.

Yang X. Applications of CRISPR-Cas9 mediated genome engineering. Mil Med Res. 2015;2:11. PMid:25984354.

Yen ST, Zhang M, Deng JM, Usman SJ, Smith CN, Parker-Thornburg J, Swinton PG, Martin JF, Behringer RR. Somatic mosaicism and allele complexity induced by CRISPR/Cas9 RNA injections in mouse zygotes. Dev Biol. 2014;393(1):3-9. http://dx.doi.org/10.1016/j.ydbio.2014.06.017. PMid:24984260.

Zafra MP, Schatoff EM, Katti A, Foronda M, Breinig M, Schweitzer AY, Simon A, Han T, Goswami S, Montgomery E, Thibado J, Kastenhuber ER, Sánchez-Rivera FJ, Shi J, Vakoc CR, Lowe SW, Tschaharganeh DF, Dow LE. Optimized base editors enable efficient editing in cells, organoids and mice. Nat Biotechnol. 2018;36(9):888-93. http://dx.doi.org/10.1038/nbt.4194. PMid:29969439.

Zhang X-H, Tee LY, Wang X-G, Huang Q-S, Yang S-H. Off-target effects in CRISPR/Cas9-mediated genome engineering. Mol Ther Nucleic Acids. 2015;4(11):e264. http://dx.doi.org/10.1038/mtna.2015.37. PMid:26575098.

Zhao S, Zhu W, Xue S, Han D. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 2014;11(5):428-37. http://dx.doi.org/10.1038/cmi.2014.38. PMid:24954222.

Zou X, Ouyang H, Yu T, Chen X, Pang D, Tang X, Chen C. Preparation of a new type 2 diabetic miniature pig model via the CRISPR/Cas9 system. Cell Death Dis. 2019;10(11):823. http://dx.doi.org/10.1038/s41419-019-2056-5. PMid:31659151.
 


Submitted date:
06/05/2023

Accepted date:
02/16/2024

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