Directions and applications of CRISPR technology in livestock research
IsmaeI Lamas-Toranzo, Priscila Ramos-Ibeas, Eva Pericuesta, Pablo Bermejo-Álvarez
Abstract
The ablation (KO) or targeted insertion (KI) of specific genes or sequences has been essential to test their roles on a particular biological process. Unfortunately, such genome modifications have been largely limited to the mouse model, as the only way to achieve targeted mutagenesis in other mammals required from somatic cell nuclear transfer, a time- and resource-consuming technique. This difficulty has left research in livestock species largely devoided of KO and targeted KI models, crucial tools to uncover the molecular roots of any physiological or pathological process. Luckily, the eruption of site-specific endonucleases, and particularly CRISPR technology, has empowered farm animal scientists to consider projects that could not develop before. In this sense, the availability of genome modification in livestock species is meant to change the way research is performed on many fields, switching from descriptive and correlational approaches to experimental research. In this review we will provide some guidance about how the genome can be edited by CRISPR and the possible strategies to achieve KO or KI, paying special attention to an initially overlooked phenomenon: mosaicism. Mosaicism is produced when the zygote´s genome edition occurs after its DNA has replicated, and is characterized by the presence of more than two alleles in the same individual, an undesirable outcome when attempting direct KO generation. Finally, the possible applications on different fields of livestock research, such as reproduction or infectious diseases are discussed.
References
Bennett GL, Leymaster KA. 1989. Integration of ovulation rate, potential embryonic viability and uterine capacity into a model of litter size in swine. J Anim Sci, 67:1230-1241.
Berg DK, van Leeuwen J, Beaumont S, Berg M, Pfeffer PL. 2010. Embryo loss in cattle between Days 7 and 16 of pregnancy. Theriogenology, 73:250-260.
Berg DK, Smith CS, Pearton DJ, Wells DN, Broadhurst R, Donnison M, Pfeffer PL. 2011. Trophectoderm lineage determination in cattle. Dev Cell, 20:244-255.
Bermejo-Alvarez P, Rizos D, Rath D, Lonergan P, Gutierrez-Adan A. 2010. Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts. Proc Natl Acad Sci U S A, 107:3394-3399.
Bermejo-Alvarez P, Ramos-Ibeas P, Park KE, Powell AP, Vansandt L, Derek B, Ramirez MA, Gutierrez-Adan A, Telugu BP. 2015. Tet-mediated imprinting erasure in H19 locus following reprogramming of spermatogonial stem cells to induced pluripotent stem cells. Sci Rep, 5:13691.
Bevacqua RJ, Fernandez-Martin R, Savy V, Canel NG, Gismondi MI, Kues WA, Carlson DF, Fahrenkrug SC, Niemann H, Taboga OA, Ferraris S, Salamone DF. 2016. Efficient edition of the bovine PRNP prion gene in somatic cells and IVF embryos using the CRISPR/Cas9 system. Theriogenology, 86:1886-1896 e1881.
Brinster RL, Braun RE, Lo D, Avarbock MR, Oram F, Palmiter RD. 1989. Targeted correction of a major histocompatibility class II E alpha gene by DNA microinjected into mouse eggs. Proc Natl Acad Sci U S A, 86:7087-7091.
Buchholz F, Angrand PO, Stewart AF. 1998. Improved properties of FLP recombinase evolved by cycling mutagenesis. Nat Biotechnol, 16:657-662.
Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, Whitelaw CB, Archibald AL. 2017. Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function. PLoS Pathog, 13:e1006206.
Capecchi MR. 1989. Altering the genome by homologous recombination. Science, 244:1288-1292.
Carlson DF, Tan W, Lillico SG, Stverakova D, Proudfoot C, Christian M, Voytas DF, Long CR, Whitelaw CB, Fahrenkrug SC. 2012. Efficient TALEN-mediated gene knockout in livestock. Proc Natl Acad Sci U S A, 109:17382-17387.
Chan AW, Homan EJ, Ballou LU, Burns JC, Bremel RD. 1998. Transgenic cattle produced by reversetranscribed gene transfer in oocytes. Proc Natl Acad Sci U S A, 95:14028-14033.
Chuang CK, Chen CH, Huang CL, Su YH, Peng SH, Lin TY, Tai HC, Yang TS, Tu CF. 2016. Generation of GGTA1 Mutant Pigs by Direct Pronuclear Microinjection of CRISPR/Cas9 Plasmid Vectors. Anim Biotechnol, 1-8.
Crispo M, Mulet AP, Tesson L, Barrera N, Cuadro F, dos Santos-Neto PC, Nguyen TH, Creneguy A, Brusselle L, Anegon I, Menchaca A. 2015. Efficient Generation of Myostatin Knock-Out Sheep Using CRISPR/Cas9 Technology and Microinjection into Zygotes. PLoS ONE, 10:e0136690.
De Frutos C, Lopez-Cardona AP, Fonseca Balvis N, Laguna-Barraza R, Rizos D, Gutierrez-Adan A, Bermejo-Alvarez P. 2016. Spermatozoa telomeres determine telomere length in early embryos and offspring. Reproduction, 151:1-7.
Doetschman T, Maeda N, Smithies O. 1988. Targeted mutation of the Hprt gene in mouse embryonic stem cells. Proc Natl Acad Sci U S A, 85:8583-8587.
Dunne LD, Diskin MG, Sreenan JM. 2000. Embryo and foetal loss in beef heifers between day 14 of gestation and full term. Anim Reprod Sci, 58:39-44.
Eid LN, Lorton SP, Parrish JJ. 1994. Paternal influence on S-phase in the first cell cycle of the bovine embryo. Biol Reprod, 51:1232-1237.
Evans MJ, Bradley A, Kuehn MR, Robertson EJ. 1985. The ability of EK cells to form chimeras after selection of clones in G418 and some observations on the integration of retroviral vector proviral DNA into EK cells. Cold Spring Harb Symp Quant Biol, 50:685- 689.
Gao Y, Wu H, Wang Y, Liu X, Chen L, Li Q, Cui C, Zhang J, Zhang Y. 2017. Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects. Genome Biol, 18:13.
Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Menoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R. 2009. Knockout rats via embryo microinjection of zinc-finger nucleases. Science, 325:433.
Gomez MC, Catt SL, Gillan L, Catt JW, Evans G, Maxwell WM. 1998. Time course of pronuclear formation and fertilisation after insemination in vitro and intracytoplasmic sperm injection of in vitro matured sheep oocytes. Zygote, 6:261-270.
Guo R, Wan Y, Xu D, Cui L, Deng M, Zhang G, Jia R, Zhou W, Wang Z, Deng K, Huang M, Wang F, Zhang Y. 2016. Generation and evaluation of Myostatin knock-out rabbits and goats using CRISPR/Cas9 system. Sci Rep, 6:29855.
Hai T, Teng F, Guo R, Li W, Zhou Q. 2014. One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res, 24:372-375.
Hammer RE, Pursel VG, Rexroad CE, Jr, Wall RJ, Bolt DJ, Ebert KM, Palmiter RD, Brinster RL. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature, 315:680-683.
Honda A, Hirose M, Sankai T, Yasmin L, Yuzawa K, Honsho K, Izu H, Iguchi A, Ikawa M, Ogura A 2015. Single-step generation of rabbits carrying a targeted allele of the tyrosinase gene using CRISPR/Cas9. Exp Anim, 64:31-37.
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012. A programmable dual-RNAguided DNA endonuclease in adaptive bacterial immunity. Science, 337:816-821.
Kang JT, Cho B, Ryu J, Ray C, Lee EJ, Yun YJ, Ahn S, Lee J, Ji DY, Jue N, Clark-Deener S, Lee K, Park KW. 2016. Biallelic modification of IL2RG leads to severe combined immunodeficiency in pigs. Reprod Biol Endocrinol, 14:74.
Kato Y, Tani T, Tsunoda Y. 2000. Cloning of calves from various somatic cell types of male and female adult, newborn and fetal cows. J Reprod Fertil, 120:231-237.
Kim BK, Cheon SH, Lee YJ, Choi SH, Cui XS, Kim NH. 2003. Pronucleus formation, DNA synthesis and metaphase entry in porcine oocytes following intracytoplasmic injection of murine spermatozoa. Zygote, 11:261-270.
Lamas-Toranzo I, Guerrero-Sánchez J, MirallesBover H, Alegre-Cid G, Pericuesta E, BermejoÁlvarez P. 2017. CRISPR is knocking on barn door. Reprod Domest Anim, 52(Suppl 4):39-47.
Laurincik J, Hyttel P, Kopecny V. 1995. DNA synthesis and pronucleus development in pig zygotes obtained in vivo: an autoradiographic and ultrastructural study. Mol Reprod Dev, 40:325-332.
Lillico SG, Proudfoot C, King TJ, Tan W, Zhang L, Mardjuki R, Paschon DE, Rebar EJ, Urnov FD, Mileham AJ, McLaren DG, Whitelaw CB. 2016. Mammalian interspecies substitution of immune modulatory alleles by genome editing. Sci Rep, 6:21645.
Lv Q, Yuan L, Deng J, Chen M, Wang Y, Zeng J, Li Z, Lai L. 2016. Efficient Generation of Myostatin Gene Mutated Rabbit by CRISPR/Cas9. Sci Rep, 6:25029.
Matas C, Coy P, Romar R, Marco M, Gadea J, Ruiz S. 2003. Effect of sperm preparation method on in vitro fertilization in pigs. Reproduction, 125:133-141.
Moehle EA, Rock JM, Lee YL, Jouvenot Y, DeKelver RC, Gregory PD, Urnov FD, Holmes MC. 2007. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. Proc Natl Acad Sci U S A, 104:3055-3060.
Mogas T, Palomo MJ, Izquierdo MD, Paramio MT. 1997. Morphological events during in vitro fertilization of prepubertal goat oocytes matured in vitro. Theriogenology, 48:815-829.
Mojica FJ, Diez-Villasenor C, Garcia-Martinez J, Soria E. 2005. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol, 60:174-182.
Moore JK, Haber JE. 1996. Cell cycle and genetic requirements of two pathways of nonhomologous endjoining repair of double-strand breaks in Saccharomyces cerevisiae. Mol Cellular Biol, 16:2164-2173.
Oprescu S, Thibault C. 1965. Duplication de l´ADN dans les oeufs de lapine après la fécondation. Ann Biol Anim Biochem Biophy, 5:151-156.
Orban PC, Chui D, Marth JD. 1992. Tissue- and sitespecific DNA recombination in transgenic mice. Proc Natl Acad Sci U S A, 89:6861-6865.
Orr-Weaver TL, Szostak JW, Rothstein RJ. 1981. Yeast transformation: a model system for the study of recombination. Proc Natl Acad Sci U S A, 78:6354- 6358.
Park KE, Powell A, Sandmaier SE, Kim CM, Mileham A, Donovan DM, Telugu BP. 2017. Targeted gene knock-in by CRISPR/Cas ribonucleoproteins in porcine zygotes. Sci Rep, 7:42458.
Parrish JJ, Susko-Parrish JL, Leibfried-Rutledge ML, Critser ES, Eyestone WH, First NL. 1986. Bovine in vitro fertilization with frozen-thawed semen. Theriogenology, 25:591-600.
Pattabiraman S, Baumann C, Guisado D, Eppig JJ, Schimenti JC, De La Fuente R. 2015. Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability. J Cell Biol, 208:53-69.
Petersen B, Frenzel A, Lucas-Hahn A, Herrmann D, Hassel P, Klein S, Ziegler M, Hadeler KG, Niemann H. 2016. Efficient production of biallelic GGTA1 knockout pigs by cytoplasmic microinjection of CRISPR/Cas9 into zygotes. Xenotransplantation, 23:338-346.
Pincus G, Enzmann EV. 1932. Fertilisation in the Rabbit. J Exp Biol, 9:403-408.
Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F. 2013a. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell, 154:1380-1389.
Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 2013b. Genome engineering using the CRISPR-Cas9 system. Nat Protoc, 8:2281-2308.
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. 2015. In vivo genome editing using Staphylococcus aureus Cas9. Nature, 520:186-191.
Santos JE, Thatcher WW, Chebel RC, Cerri RL, Galvao KN. 2004. The effect of embryonic death rates in cattle on the efficacy of estrus synchronization programs. Anim Reprod Sci, 82-83:513-535.
Sato M, Koriyama M, Watanabe S, Ohtsuka M, Sakurai T, Inada E, Saitoh I, Nakamura S, Miyoshi K. 2015. Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations. Int J Mol Sci, 16:17838-17856.
Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I, Colman A, Campbell KH. 1997. Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science, 278:2130-2133.
Shemesh M, Gurevich M, Harel-Markowitz E, Benvenisti L, Shore LS, Stram Y. 2000. Gene integration into bovine sperm genome and its expression in transgenic offspring. Mol Reprod Dev, 56:306-308.
Shen B, Zhang J, Wu H, Wang J, Ma K, Li Z, Zhang X, Zhang P, Huang X. 2013. Generation of genemodified mice via Cas9/RNA-mediated gene targeting. Cell Res, 23:720-723.
Sheridan C. 2016. FDA approves 'farmaceutical' drug from transgenic chickens. Nat Biotechnol, 34:117-119.
Singh P, Schimenti JC, Bolcun-Filas E. 2015. A mouse geneticist's practical guide to CRISPR applications. Genetics, 199:1-15.
Song J, Yang D, Xu J, Zhu T, Chen YE, Zhang J. 2016a. RS-1 enhances CRISPR/Cas9- and TALENmediated knock-in efficiency. Nat Commun, 7:10548.
Song Y, Yuan L, Wang Y, Chen M, Deng J, Lv Q, Sui T, Li Z, Lai L. 2016b. Efficient dual sgRNAdirected large gene deletion in rabbit with CRISPR/Cas9 system. Cell Mol Life Sci, 73:2959-2968.
Spencer LT, Humphries JE, Brantly ML. 2005. Antibody response to aerosolized transgenic human alpha1-antitrypsin. N Engl J Med, 352:2030-2031.
Sui T, Yuan L, Liu H, Chen M, Deng J, Wang Y, Li Z, Lai L. 2016. CRISPR/Cas9-mediated mutation of PHEX in rabbit recapitulates human X-linked hypophosphatemia (XLH). Hum Mol Genet, 25:2661- 2671.
Szollosi D. 1966. Time and duration of DNA synthesis in rabbit eggs after sperm penetration. Anat Rec, 154:209-212.
Tan W, Carlson DF, Lancto CA, Garbe JR, Webster DA, Hackett PB, Fahrenkrug SC. 2013. Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proc Natl Acad Sci U S A, 110:16526-16531.
Tesson L, Usal C, Menoret S, Leung E, Niles BJ, Remy S, Santiago Y, Vincent AI, Meng X, Zhang L, Gregory PD, Anegon I, Cost GJ. 2011. Knockout rats generated by embryo microinjection of TALENs. Nat Biotechnol, 29:695-696.
Van Eenennaam AL. 2018. The importance of a novel product risk-based trigger for gene editing regulation in food animal species. The CRISPR Journal, 1. https://doi.org/10.1089/crispr.2017.0023 van Veen HA, Koiter J, Vogelezang CJ, van Wessel N, van Dam T, Velterop I, van Houdt K, Kupers L, Horbach D, Salaheddine M, Nuijens JH, Mannesse ML. 2012. Characterization of recombinant human C1 inhibitor secreted in milk of transgenic rabbits. J Biotechnol, 162:319-326.
Vilarino M, Rashid ST, Suchy FP, McNabb BR, van der Meulen T, Fine EJ, Ahsan S, Mursaliyev N, Sebastiano V, Diab SS, Huising MO, Nakauchi H, Ross PJ. 2017. CRISPR/Cas9 microinjection in oocytes disables pancreas development in sheep. Sci Rep, 7:17472.
Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. 2013. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell, 153:910-918.
Wang K, Ouyang H, Xie Z, Yao C, Guo N, Li M, Jiao H, Pang D. 2015a. Efficient Generation of Myostatin Mutations in Pigs Using the CRISPR/Cas9 System. Sci Rep, 5:16623.
Wang X, Yu H, Lei A, Zhou J, Zeng W, Zhu H, Dong Z, Niu Y, Shi B, Cai B, Liu J, Huang S, Yan H, Zhao X, Zhou G, He X, Chen X, Yang Y, Jiang Y, Shi L, Tian X, Wang Y, Ma B, Huang X, Qu L, Chen Y. 2015b. Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system. Sci Rep, 5:13878.
Wang Y, Du Y, Shen B, Zhou X, Li J, Liu Y, Wang J, Zhou J, Hu B, Kang N, Gao J, Yu L, Huang X, Wei H. 2015c. Efficient generation of gene-modified pigs via injection of zygote with Cas9/sgRNA. Sci Rep, 5:8256.
Wang X, Cai B, Zhou J, Zhu H, Niu Y, Ma B, Yu H, Lei A, Yan H, Shen Q, Shi L, Zhao X, Hua J, Huang X, Qu L, Chen Y. 2016a. Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers. PLoS ONE, 11:e0164640.
Wang X, Cao C, Huang J, Yao J, Hai T, Zheng Q, Zhang H, Qin G, Cheng J, Wang Y, Yuan Z, Zhou Q, Wang H, Zhao J. 2016b. One-step generation of triple gene-targeted pigs using CRISPR/Cas9 system. Sci Rep, 6:20620.
Wang X, Niu Y, Zhou J, Yu H, Kou Q, Lei A, Zhao X, Yan H, Cai B, Shen Q, Zhou S, Zhu H, Zhou G, Niu W, Hua J, Jiang Y, Huang X, Ma B, Chen Y. 2016c. Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. Sci Rep, 6:32271.
Whitelaw CB, Sheets TP, Lillico SG, Telugu BP. 2016. Engineering large animal models of human disease. J Pathol, 238:247-256.
Whitworth KM, Rowland RR, Ewen CL, Trible BR, Kerrigan MA, Cino-Ozuna AG, Samuel MS, Lightner JE, McLaren DG, Mileham AJ, Wells KD, Prather RS. 2016. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nat Biotechnol, 34:20-22.
Whitworth KM, Benne JA, Spate LD, Murphy SL, Samuel MS, Murphy CN, Richt JA, Walters E, Prather RS, Wells KD. 2017. Zygote injection of CRISPR/Cas9 RNA successfully modifies the target gene without delaying blastocyst development or altering the sex ratio in pigs. Transgenic Res, 26:97- 107.
Whyte JJ, Prather RS. 2011. Genetic modifications of pigs for medicine and agriculture. Mol Reprod Dev, 78:879-891.
Whyte JJ, Zhao J, Wells KD, Samuel MS, Whitworth KM, Walters EM, Laughlin MH, Prather RS. 2011. Gene targeting with zinc finger nucleases to produce cloned eGFP knockout pigs. Mol Reprod Deve, 78:2.
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature, 385:810-813.
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, Vilarino M, Parrilla I, Soto DA, Martinez CA, Hishida T, Sanchez-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, Nunez Delicado E, Lajara J, Guillen I, Guillen P, Campistol JM, Martinez EA, Ross PJ, Izpisua Belmonte JC. 2017. Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell, 168:473- 486 e415.
Yan Q, Zhang Q, Yang H, Zou Q, Tang C, Fan N, Lai L. 2014. Generation of multi-gene knockout rabbits using the Cas9/gRNA system. Cell Regen, 3:12.
Yang D, Song J, Zhang J, Xu J, Zhu T, Wang Z, Lai L, Chen YE. 2016. Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression. Sci Rep, 6:25161.
Yang H, Wang H, Jaenisch R. 2014. Generating genetically modified mice using CRISPR/Cas-mediated genome engineering. Nature protocols, 9:1956-1968.
Yu HH, Zhao H, Qing YB, Pan WR, Jia BY, Zhao HY, Huang XX, Wei HJ. 2016. Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy. Int J Mol Sci, 17: Yuan L, Sui T, Chen M, Deng J, Huang Y, Zeng J, Lv Q, Song Y, Li Z, Lai L. 2016. CRISPR/Cas9- mediated GJA8 knockout in rabbits recapitulates human congenital cataracts. Sci Rep, 6:22024.
Zhang X, Li W, Wu Y, Peng X, Lou B, Wang L, Liu M. 2017. Disruption of the sheep BMPR-IB gene by CRISPR/Cas9 in in vitro-produced embryos. Theriogenology, 91:163-172 e162.
Zhou X, Wang L, Du Y, Xie F, Li L, Liu Y, Liu C, Wang S, Zhang S, Huang X, Wang Y, Wei H. 2016. Efficient Generation of Gene-Modified Pigs Harboring Precise Orthologous Human Mutation via CRISPR/Cas9-Induced Homology-Directed Repair in Zygotes. Hum Mutat, 37:110-118.
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