Effect of genetic background on glycosylation heterogeneity in human antithrombin produced in the mammary gland of transgenic goats

Zhou, Qun; Kyazike, Josephine; Echelard, Yann; Meade, Harry; Higgins, Elizabeth; Cole, Edward S.; Edmunds, Tim

doi:10.1016/j.jbiotec.2005.01.001

Cited by 45 publications

(27 citation statements)

References 22 publications

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“…Sialylation level decreased with the progress of lactation independent of glycoprotein expression levels in accordance with earlier data reported for a few native human and bovine milk glycoproteins [43,44]. Recombinant preparations of human anti-thrombin expressed in the milk of transgenic goats have been reported by Edmunds et al [6] and Zhou et al [45] to contain GalNAc-GlcNAc epitopes and to show variable relationships between protein expression and glycosylation. Goats expressing high levels of hAnti-thrombin (12.5 g/L) showed less heterogeneity in the N-glycan profiles than animals with low levels of expression.…”

Section: Discussionsupporting

confidence: 88%

Monosialylated biantennary N-glycoforms containing GalNAc–GlcNAc antennae predominate when human EPO is expressed in goat milk

Montesino

Toledo

Sánchez

et al. 2008

Archives of Biochemistry and Biophysics

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Recently, our group reported the expression of recombinant human erythropoietin in goat milk (rhEPO-milk) as well as in the mammary epithelial cell line GMGE (EPO-GMGE) by cell culture using the adenoviral transduction system. N-Glycosylation characterization of rhEPO-milk by Normal-Phase HPLC profiling of the fluorophore, 4-aminobenzoic acid-labeled enzymatically released N-glycan pool from rhEPO-goat milk, combined with MALDI, ESI-MS and LC/MS, revealed that low branched, core-fucosylated, N-glycans predominate. The labeled N-glycans were separated into neutral and charged fractions by anion exchange chromatography and the charged N-glycans were found to be mostly a2,6-monosialylated with Neu5Ac or Neu5Gc in a ratio of 1:1. Unlike the N-glycans from rhEPO produced in CHO cells, where the glycans are multiantennary highly sialylated, core-fucosylated oligosaccahrides, or even in the goat mammary gland epithelial cell line cultured in vitro in which multiantennary, core-and outer-arm fucosylated, monosialylated Nglycans are the most abundant species, a large proportion of the N-glycans from rhEPO-milk were monosialylated, biantennary, antennae mostly terminating with the more unusual GalNAc-GlcNAc motive and without outer-arm fucosylation. These findings, emphasizing the difference in the N-glycan repertoire between the rhEPO-milk and EPO-GMGE, are consistent with the principle that glycosylation is cell-type dependent and that the cell environment is crucial as well.

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Section: Discussionsupporting

confidence: 88%

Monosialylated biantennary N-glycoforms containing GalNAc–GlcNAc antennae predominate when human EPO is expressed in goat milk

Montesino

Toledo

Sánchez

et al. 2008

Archives of Biochemistry and Biophysics

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“…In addition, a number of different proteins derived from the blood of transgenic animals are in various stages of development. The vital blood products can be utilized in various forms such as clotting factors, antithrombin [1][2][3][4] and human albumin 5,6 . Actually 'ATryn' was the first product approved in U.S. from a genetically engineered animal and had been granted orphan drug status by the FDA for the treatment of hereditary antithrombin deficiency.…”

Section: Potential Benefits Of Genetically Engineering Animalsmentioning

confidence: 99%

Genetically Engineered Animals and their Intended Uses in Day to Day Life

Singh¹,

Sachan²

2015

Science International

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Background:Genetically engineering is an integral approach to the development of new diagnostic techniques, drugs for human and animal diseases, foods for human health, development of tissues and cells for xenotransplantation. The components of vaccine for disease control and nutraceuticals for human health by altering the food components or by introducing the health provide proteins, peptides and other components may be the integral part of human life in coming days. Genetically engineered animals also offer significant human health and environmental benefits, livestock becomes more efficient for converting feed to animal protein and reducing waste production. Finally, genetic engineering will improve the welfare of animals by imparting resistance to disease and enhancing overall health and well being. Objective: This study reviews the basics of genetic engineering and their scope in various fields of life. Conclusion:The need is to commercialize the technology by the authentication on science based formulations. The judicial approaches and validation of the technologies by removing the myths related to the technology are some other issues must be handled properly.

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“…Not until then can such purified pharmaceuticals of recombinant human α 1 -AT synthesized by udder bioreactors of genetically-engineered cloned ruminants be used in clinical programs involving substitutional therapy and multipreventive prophylaxis not only for different variants of emphysema, but also for mucoviscidosis (cystic fibrosis), another hereditary mono-gene disease of the respiratory epithelium in pulmonary alveoli and bronchi (McCreath et al 2000, Boaglio et al 2006. In turn, recombinant human antithrombin III-α, which has been extracted from the milk or beestings of transgenic SCNT-derived livestock species, could be applied as a blood anticoagulation agent (inhibitor of thrombin activity) in cardiologic surgery (Baguisi et al 1999, Zhou et al 2005.…”

Section: Advantages Of the Use Of Somatic Cell Cloning In Generating mentioning

confidence: 99%

Transgenic mammalian species, generated by somatic cell cloning, in biomedicine, biopharmaceutical industry and human nutrition/dietetics - recent achievements

Samiec¹,

Skrzyszowska²

2011

Polish Journal of Veterinary Sciences

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Somatic cell cloning technology in mammals promotes the multiplication of productively-valuable genetically engineered individuals, and consequently allows also for standardization of transgenic farm animal-derived products, which, in the context of market requirements, will have growing significance. Gene farming is one of the most promising areas in modern biotechnology. The use of live bioreactors for the expression of human genes in the lactating mammary gland of transgenic animals seems to be the most cost-effective method for the production/processing of valuable recombinant therapeutic proteins. Among the transgenic farm livestock species used so far, cattle, goats, sheep, pigs and rabbits are useful candidates for the expression of tens to hundreds of grams of genetically-engineered proteins or xenogeneic biopreparations in the milk. At the beginning of the new millennium, a revolution in the treatment of disease is taking shape due to the emergence of new therapies based on recombinant human proteins. The ever-growing demand for such pharmaceutical or nutriceutical proteins is an important driving force for the development of safe and large-scale production platforms. The aim of this paper is to present an overall survey of the state of the art in investigations which provide the current knowledge for deciphering the possibilities of practical application of the transgenic mammalian species generated by somatic cell cloning in biomedicine, the biopharmaceutical industry, human nutrition/dietetics and agriculture.

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Effect of genetic background on glycosylation heterogeneity in human antithrombin produced in the mammary gland of transgenic goats

Cited by 45 publications

References 22 publications

Monosialylated biantennary N-glycoforms containing GalNAc–GlcNAc antennae predominate when human EPO is expressed in goat milk

Monosialylated biantennary N-glycoforms containing GalNAc–GlcNAc antennae predominate when human EPO is expressed in goat milk

Genetically Engineered Animals and their Intended Uses in Day to Day Life

Transgenic mammalian species, generated by somatic cell cloning, in biomedicine, biopharmaceutical industry and human nutrition/dietetics - recent achievements

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