title: Production of Human Albumin in Pigs Through CRISPR/Cas9-Mediated Knockin of Human cDNA into Swine Albumin Locus in the Zygotes.
abstract: Precise genome modification in large domesticated animals is desirable under many circumstances. In the past it is only possible through lengthy and burdensome cloning procedures. Here we attempted to achieve that goal through the use of the newest genome-modifying tool CRISPR/Cas9. We set out to knockin human albumin cDNA into pig Alb locus for the production of recombinant human serum albumin (rHSA). HSA is a widely used human blood product and is in high demand. We show that homologous recombination can occur highly efficiently in swine zygotes. All 16 piglets born from the manipulated zygotes carry the expected knockin allele and we demonstrated the presence of human albumin in the blood of these piglets. Furthermore, the knockin allele was successfully transmitted through germline. This success in precision genomic engineering is expected to spur exploration of pigs and other large domesticated animals to be used as bioreactors for the production of biomedical products or creation of livestock strains with more desirable traits.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Science and Technology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Center for Reproductive Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Model Animal Research Center, Nanjing University, Nanjing, Jiangsu Province 210061, China.
authors.forename: Xingxu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, Life Sciences Park, Beijing 102206, China.
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D000818:Animals; D064113:CRISPR-Cas Systems; D018076:DNA, Complementary; D015870:Gene Expression; D055879:Gene Knock-In Techniques; D023061:Gene Order; D018390:Gene Targeting; D056426:Genetic Loci; D006801:Humans; D012709:Serum Albumin / Q000096:biosynthesis* / Q000235:genetics*; D013552:Swine; D015053:Zygote / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D012709:Serum Albumin