Cloned transchromosomic calves producing human immunoglobulin

Yoshimi Kuroiwa; Poothappillai Kasinathan; Yoon J. Choi; Rizwan Naeem; Kazuma Tomizuka; Eddie J. Sullivan; Jason G. Knott; Anae Duteau; Richard A. Goldsby; Barbara A. Osborne; Isao Ishida; James M. Robl

doi:10.1038/nbt727

Cloned transchromosomic calves producing human immunoglobulin

Yoshimi Kuroiwa, Poothappillai Kasinathan, Yoon J. Choi, Rizwan Naeem, Kazuma Tomizuka, Eddie J. Sullivan, Jason G. Knott, Anae Duteau, Richard A. Goldsby, Barbara A. Osborne, Isao Ishida, James M. Robl

Research output: Contribution to journal › Article › peer-review

205 Scopus citations

Abstract

Human polyclonal antibodies (hPABs) are useful therapeutics, but because they are available only from human donors, their supply and application is limited. To address this need, we prepared a human artificial chromosome (HAC) vector containing the entire unrearranged sequences of the human immunoglobulin (h/g) heavy-chain (H) and lambda (λ) light-chain loci. The HAC vector was introduced into bovine primary fetal fibroblasts using a microcell-mediated chromosome transfer (MMCT) approach. Primary selection was carried out, and the cells were used to produce cloned bovine fetuses. Secondary selection was done on the regenerated fetal cell lines, which were then used to produce four healthy transchromosomic (Tc) calves. The HAC was retained at a high rate (78-100% of cells) in calves and the h/g loci underwent rearrangement and expressed diversified transcripts. Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs.

Original language	English (US)
Pages (from-to)	889-894
Number of pages	6
Journal	Nature biotechnology
Volume	20
Issue number	9
DOIs	https://doi.org/10.1038/nbt727
State	Published - Sep 2002
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/nbt727

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title = "Cloned transchromosomic calves producing human immunoglobulin",

abstract = "Human polyclonal antibodies (hPABs) are useful therapeutics, but because they are available only from human donors, their supply and application is limited. To address this need, we prepared a human artificial chromosome (HAC) vector containing the entire unrearranged sequences of the human immunoglobulin (h/g) heavy-chain (H) and lambda (λ) light-chain loci. The HAC vector was introduced into bovine primary fetal fibroblasts using a microcell-mediated chromosome transfer (MMCT) approach. Primary selection was carried out, and the cells were used to produce cloned bovine fetuses. Secondary selection was done on the regenerated fetal cell lines, which were then used to produce four healthy transchromosomic (Tc) calves. The HAC was retained at a high rate (78-100% of cells) in calves and the h/g loci underwent rearrangement and expressed diversified transcripts. Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs.",

author = "Yoshimi Kuroiwa and Poothappillai Kasinathan and Choi, {Yoon J.} and Rizwan Naeem and Kazuma Tomizuka and Sullivan, {Eddie J.} and Knott, {Jason G.} and Anae Duteau and Goldsby, {Richard A.} and Osborne, {Barbara A.} and Isao Ishida and Robl, {James M.}",

note = "Funding Information: Acknowledgments We thank J. Pommer, J. Koster, J. Molina, and D. Faber at Trans Ova Genetics for their assistance with animals and T. King and M. Nichols for their assistance in nuclear transplantation. Partial support for work in the laboratory of R.A.G. was contributed by National Science Foundation grant NSF-MCB-9986213.",

year = "2002",

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doi = "10.1038/nbt727",

language = "English (US)",

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pages = "889--894",

journal = "Nature biotechnology",

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AU - Kuroiwa, Yoshimi

AU - Kasinathan, Poothappillai

AU - Choi, Yoon J.

AU - Naeem, Rizwan

AU - Tomizuka, Kazuma

AU - Sullivan, Eddie J.

AU - Knott, Jason G.

AU - Duteau, Anae

AU - Goldsby, Richard A.

AU - Osborne, Barbara A.

AU - Ishida, Isao

AU - Robl, James M.

N1 - Funding Information: Acknowledgments We thank J. Pommer, J. Koster, J. Molina, and D. Faber at Trans Ova Genetics for their assistance with animals and T. King and M. Nichols for their assistance in nuclear transplantation. Partial support for work in the laboratory of R.A.G. was contributed by National Science Foundation grant NSF-MCB-9986213.

PY - 2002/9

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N2 - Human polyclonal antibodies (hPABs) are useful therapeutics, but because they are available only from human donors, their supply and application is limited. To address this need, we prepared a human artificial chromosome (HAC) vector containing the entire unrearranged sequences of the human immunoglobulin (h/g) heavy-chain (H) and lambda (λ) light-chain loci. The HAC vector was introduced into bovine primary fetal fibroblasts using a microcell-mediated chromosome transfer (MMCT) approach. Primary selection was carried out, and the cells were used to produce cloned bovine fetuses. Secondary selection was done on the regenerated fetal cell lines, which were then used to produce four healthy transchromosomic (Tc) calves. The HAC was retained at a high rate (78-100% of cells) in calves and the h/g loci underwent rearrangement and expressed diversified transcripts. Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs.

AB - Human polyclonal antibodies (hPABs) are useful therapeutics, but because they are available only from human donors, their supply and application is limited. To address this need, we prepared a human artificial chromosome (HAC) vector containing the entire unrearranged sequences of the human immunoglobulin (h/g) heavy-chain (H) and lambda (λ) light-chain loci. The HAC vector was introduced into bovine primary fetal fibroblasts using a microcell-mediated chromosome transfer (MMCT) approach. Primary selection was carried out, and the cells were used to produce cloned bovine fetuses. Secondary selection was done on the regenerated fetal cell lines, which were then used to produce four healthy transchromosomic (Tc) calves. The HAC was retained at a high rate (78-100% of cells) in calves and the h/g loci underwent rearrangement and expressed diversified transcripts. Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs.

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Cloned transchromosomic calves producing human immunoglobulin

Abstract

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