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 journalArticle

185 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 languageEnglish (US)
Pages (from-to)889-894
Number of pages6
JournalNature biotechnology
Volume20
Issue number9
DOIs
StatePublished - Sep 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Cite this

Kuroiwa, Y., Kasinathan, P., Choi, Y. J., Naeem, R., Tomizuka, K., Sullivan, E. J., Knott, J. G., Duteau, A., Goldsby, R. A., Osborne, B. A., Ishida, I., & Robl, J. M. (2002). Cloned transchromosomic calves producing human immunoglobulin. Nature biotechnology, 20(9), 889-894. https://doi.org/10.1038/nbt727