Reflections on the system of evaluation of gene-edited livestock

Abstract

The rapid development of biotechnology has provided a greater understanding of the biological functions of major candidate genes that have important functions regarding economic traits, and new materials for livestock breeding have been obtained through gene editing (GE) and embryo manipulation with the purpose of improving quality and output and reducing the costs and risk of disease. Public concerns, particularly over safety risks and production performance, must be addressed. Evaluation is the most important component of the regulation of gene-edited livestock and is a crucial guarantee of public safety before the marketing of gene-edited animal products. Here, the system of evaluation of gene-edited livestock is discussed in terms of public safety and production performance. The search for safe and ethical applications in the GE of livestock, a case-by-case evaluation strategy, and classification and simplification are used in order to promote a more efficient, objective, comprehensive and operable evaluation system.

Keywords

evaluation / gene editing / livestock / performance / safety

References

[1] Costantini F, Lacy E. Introduction of a rabbit β-globin gene into the mouse germ line. Nature, 1981, 294(5836): 92–94

[2] Hammer R E, Pursel V G, Rexroad C E Jr, Wall R J, Bolt D J, Ebert K M, Palmiter R D, Brinster R L. Production of transgenic rabbits, sheep and pigs by microinjection. Nature, 1985, 315(6021): 680–683

[3] Maga E A, Geoffrey Sargent R, Zeng H, Pati S, Zarling D A, Oppenheim S M, Collette N M B, Moyer A L, Conrad-Brink J S, Rowe J D, BonDurant R H, Anderson G B, Murray J D. Increased efficiency of transgenic livestock production. Transgenic Research, 2003, 12(4): 485–496

[4] Carlson D F, Tan W, Lillico S G, Stverakova D, Proudfoot C, Christian M, Voytas D F, Long C R, Whitelaw C B, Fahrenkrug S C. Efficient TALEN-mediated gene knockout in livestock. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(43): 17382–17387

[5] Bibikova M, Beumer K, Trautman J K, Carroll D. Enhancing gene targeting with designed zinc finger nucleases. Science, 2003, 300(5620): 764

[6] Miller J C, Holmes M C, Wang J, Guschin D Y, Lee Y L, Rupniewski I, Beausejour C M, Waite A J, Wang N S, Kim K A, Gregory P D, Pabo C O, Rebar E J. An improved zinc-finger nuclease architecture for highly specific genome editing. Nature Biotechnology, 2007, 25(7): 778–785

[7] Wood A J, Lo T W, Zeitler B, Pickle C S, Ralston E J, Lee A H, Amora R, Miller J C, Leung E, Meng X, Zhang L, Rebar E J, Gregory P D, Urnov F D, Meyer B J. Targeted genome editing across species using ZFNs and TALENs. Science, 2011, 333(6040): 307

[8] Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna J A, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 2012, 337(6096): 816–821

[9] Cong L, Ran F A, Cox D, Lin S, Barretto R, Habib N, Hsu P D, Wu X, Jiang W, Marraffini L A, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science, 2013, 339(6121): 819–823

[10] Miller J C, Tan S, Qiao G, Barlow K A, Wang J, Xia D F, Meng X, Paschon D E, Leung E, Hinkley S J, Dulay G P, Hua K L, Ankoudinova I, Cost G J, Urnov F D, Zhang H S, Holmes M C, Zhang L, Gregory P D, Rebar E J. A TALE nuclease architecture for efficient genome editing. Nature Biotechnology, 2011, 29(2): 143–148

[11] Rouet P, Smih F, Jasin M. Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America, 1994, 91(13): 6064–6068

[12] Whyte J J, Zhao J, Wells K D, Samuel M S, Whitworth K M, Walters E M, Laughlin M H, Prather R S. Gene targeting with zinc finger nucleases to produce cloned eGFP knockout pigs. Molecular Reproduction and Development, 2011, 78(1): 2

[13] Qian L, Tang M, Yang J, Wang Q, Cai C, Jiang S, Li H, Jiang K, Gao P, Ma D, Chen Y, An X, Li K, Cui W. Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs. Scientific Reports, 2015, 5(1): 14435

[14] Yu B, Lu R, Yuan Y, Zhang T, Song S, Qi Z, Shao B, Zhu M, Mi F, Cheng Y. Efficient TALEN-mediated myostatin gene editing in goats. BMC Developmental Biology, 2016, 16(1): 26

[15] 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. Correction: disruption of FGF5 in Cashmere goats using CRISPR/Cas9 results in more secondary hair follicles and longer fibers. PLoS One, 2016, 11(11): e0167322

[16] Burkard C, Lillico S G, Reid E, Jackson B, Mileham A J, Ait-Ali T, Whitelaw C B A, Archibald A L. 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 Pathogens, 2017, 13(2): e1006206

[17] Gandhi P T, Athmaram T N, Arunkumar G R. Novel nicotine analogues with potential anti-mycobacterial activity. Bioorganic & Medicinal Chemistry, 2016, 24(8): 1637–1647

[18] Wu H, Wang Y, Zhang Y, Yang M, Lv J, Liu J, Zhang Y. TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(13): E1530–E1539

[19] Yu S, Luo J, Song Z, Ding F, Dai Y, Li N. Highly efficient modification of β-lactoglobulin (BLG) gene via zinc-finger nucleases in cattle. Cell Research, 2011, 21(11): 1638–1640

[20] Zhang J, Cui M L, Nie Y W, Dai B, Li F R, Liu D J, Liang H, Cang M. CRISPR/Cas9-mediated specific integration of fat-1 at the goat MSTN locus. FEBS Journal, 2018, 285(15): 2828–2839

[21] Carlson D F, Lancto C A, Zang B, Kim E S, Walton M, Oldeschulte D, Seabury C, Sonstegard T S, Fahrenkrug S C. Production of hornless dairy cattle from genome-edited cell lines. Nature Biotechnology, 2016, 34(5): 479–481

[22] Li M, Ouyang H, Yuan H, Li J, Xie Z, Wang K, Yu T, Liu M, Chen X, Tang X, Jiao H, Pang D. Site-specific fat-1 knock-in enables significant decrease of n-6PUFAs/n-3PUFAs ratio in pigs. Genetics, 2018, 8(5): 1747–1754

[23] Garas L C, Murray J D, Maga E A. Genetically engineered livestock: ethical use for food and medical models. Annual Review of Animal Biosciences, 2015, 3(1): 559–575

[24] Zhang X H, Tee L Y, Wang X G, Huang Q S, Yang S H. Off-target effects in CRISPR/Cas9-mediated genome engineering. Molecular Therapy. Nucleic Acids, 2015, 4: e264

[25] Fu Y, Sander J D, Reyon D, Cascio V M, Joung J K. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nature Biotechnology, 2014, 32(3): 279–284

[26] Zhang J H, Adikaram P, Pandey M, Genis A, Simonds W F. Optimization of genome editing through CRISPR-Cas9 engineering. Bioengineered, 2016, 7(3): 166–174

[27] Pattanayak V, Lin S, Guilinger J P, Ma E, Doudna J A, Liu D R. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nature Biotechnology, 2013, 31(9): 839–843

[28] Fu Y, Foden J A, Khayter C, Maeder M L, Reyon D, Joung J K, Sander J D. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nature Biotechnology, 2013, 31(9): 822–826

[29] Cho S W, Kim S, Kim Y, Kweon J, Kim H S, Bae S, Kim J S. Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Research, 2014, 24(1): 132–141

[30] Anzalone A V, Randolph P B, Davis J R, Sousa A A, Koblan L W, Levy J M, Chen P J, Wilson C, Newby G A, Raguram A, Liu D R. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature, 2019, 576(7785): 149–157

[31] Maga E A, Murray J D. Welfare applications of genetically engineered animals for use in agriculture. Journal of Animal Science, 2010, 88(4): 1588–1591

[32] Duensing N, Sprink T, Parrott W A, Fedorova M, Lema M A, Wolt J D, Bartsch D. Novel features and considerations for ERA and regulation of crops produced by genome editing. Frontiers in Bioengineering and Biotechnology, 2018, 6: 79

[33] Norris A L, Lee S S, Greenlees K J, Tadesse D A, Miller M F, Lombardi H A. Template plasmid integration in germline genome-edited cattle. Nature Biotechnology, 2020, 38(2): 163–164

Acknowledgements

This work was supported by the National Transgenic Project (2016ZX08006-001), the China Postdoctoral Science Foundation (2018M631648), and the Central Public Interest Scientific Institution Basal Research Fund (2018-YWF-YTS-13).

Compliance with ethics guidelines

Ziyao Fan, Tianwen Wu, Kui Xu, Yulian Mu, and Kui Li declare that they have no conflicts of interest or financial conflicts to disclose.

This article is a review and does not contain any studies with human or animal subjects performed by any of the authors.

RIGHTS & PERMISSIONS

The Author(s) 2020. Published by Higher Education Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)