YEARS

2004-2007

AUTHORS

Harry M Meade

TITLE

Improved yield of human albumin from transgenic cow milk

ABSTRACT

DESCRIPTION (provided by applicant): The overall goal of this program is to provide an abundant, cost-effective, biosecure source of human albumin for human therapeutic use by producing recombinant human albumin (rhA) in the milk of transgenic cows. Human albumin is isolated from donated human plasma, but shifts in the plasma fractionation industry, concerns about cost and anxiety about blood safety have motivated efforts to produce recombinant human albumin as an alternative source for human therapeutic applications. GTC Biotherapeutics Inc. (GTC-Bio) has expressed rhA in transgenic cows at levels of 2 g/L, which is adequate for the pharmaceutical excipient market but not the 400,000 kg annual worldwide therapeutic market. We have developed a strategy for selectively boosting rhA production to 10 g/L, a level that would make this production platform commercially feasible for the therapeutic human albumin market. Preliminary work suggests that hypermethylation of CpG motifs in the coding sequence may limit rhA expression in transgenic animals, and that removing CpG sites without altering the albumin amino acid sequence may significantly increase rhA expression. In this Fast-Track Phase I project, we propose to establish proof of principle for high-level production of rhA by: 1) remodeling the rhA gene to remove CpG sites; 2) evaluating the remodeled construct in transgenic mice, our standard test system; 3) optimizing a novel high-throughput screening method that will substantially reduce the effort and cost of recovering transgenic cell lines for use in generating transgenic animals by somatic cell nuclear transfer; and 4) optimizing an alternative selection scheme to preferentially recover transfected cell lines with high transgene copy numbers. Successful completion of this project will lead to a Fast-Track Phase II project to produce and characterize transgenic calves producing high levels of rhA in their milk. If this program is successful, it will be the first production of rhA at a commercial scale that is cost-effective for therapeutic applications.

FUNDED PUBLICATIONS

  • Production of recombinant albumin by a herd of cloned transgenic cattle
  • Production of recombinant albumin by a herd of cloned transgenic cattle.
  • How to use: Click on a object to move its position. Double click to open its homepage. Right click to preview its contents.

    Download the RDF metadata as:   json-ld nt turtle xml License info


    19 TRIPLES      17 PREDICATES      20 URIs      9 LITERALS

    Subject Predicate Object
    1 grants:e60d44553ef2be20c5fe615158769e52 sg:abstract DESCRIPTION (provided by applicant): The overall goal of this program is to provide an abundant, cost-effective, biosecure source of human albumin for human therapeutic use by producing recombinant human albumin (rhA) in the milk of transgenic cows. Human albumin is isolated from donated human plasma, but shifts in the plasma fractionation industry, concerns about cost and anxiety about blood safety have motivated efforts to produce recombinant human albumin as an alternative source for human therapeutic applications. GTC Biotherapeutics Inc. (GTC-Bio) has expressed rhA in transgenic cows at levels of 2 g/L, which is adequate for the pharmaceutical excipient market but not the 400,000 kg annual worldwide therapeutic market. We have developed a strategy for selectively boosting rhA production to 10 g/L, a level that would make this production platform commercially feasible for the therapeutic human albumin market. Preliminary work suggests that hypermethylation of CpG motifs in the coding sequence may limit rhA expression in transgenic animals, and that removing CpG sites without altering the albumin amino acid sequence may significantly increase rhA expression. In this Fast-Track Phase I project, we propose to establish proof of principle for high-level production of rhA by: 1) remodeling the rhA gene to remove CpG sites; 2) evaluating the remodeled construct in transgenic mice, our standard test system; 3) optimizing a novel high-throughput screening method that will substantially reduce the effort and cost of recovering transgenic cell lines for use in generating transgenic animals by somatic cell nuclear transfer; and 4) optimizing an alternative selection scheme to preferentially recover transfected cell lines with high transgene copy numbers. Successful completion of this project will lead to a Fast-Track Phase II project to produce and characterize transgenic calves producing high levels of rhA in their milk. If this program is successful, it will be the first production of rhA at a commercial scale that is cost-effective for therapeutic applications.
    2 sg:endYear 2007
    3 sg:fundingAmount 692691.0
    4 sg:fundingCurrency USD
    5 sg:hasContribution contributions:c47f26175a94ebc60e0f4d3dc72bacfd
    6 sg:hasFieldOfResearchCode anzsrc-for:10
    7 anzsrc-for:1004
    8 sg:hasFundedPublication articles:70266329d5ec0f8a42b635178a4ee4f9
    9 articles:e7b9bf911903c2882b6d94c5ce9515dc
    10 sg:hasFundingOrganization grid-institutes:grid.279885.9
    11 sg:hasRecipientOrganization grid-institutes:grid.420525.4
    12 sg:language English
    13 sg:license http://scigraph.springernature.com/explorer/license/
    14 sg:scigraphId e60d44553ef2be20c5fe615158769e52
    15 sg:startYear 2004
    16 sg:title Improved yield of human albumin from transgenic cow milk
    17 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=7028160
    18 rdf:type sg:Grant
    19 rdfs:label Grant: Improved yield of human albumin from transgenic cow milk
    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular JSON format for linked data.

    curl -H 'Accept: application/ld+json' 'http://scigraph.springernature.com/things/grants/e60d44553ef2be20c5fe615158769e52'

    N-Triples is a line-based linked data format ideal for batch operations .

    curl -H 'Accept: application/n-triples' 'http://scigraph.springernature.com/things/grants/e60d44553ef2be20c5fe615158769e52'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'http://scigraph.springernature.com/things/grants/e60d44553ef2be20c5fe615158769e52'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'http://scigraph.springernature.com/things/grants/e60d44553ef2be20c5fe615158769e52'






    Preview window. Press ESC to close (or click here)


    ...