Expression Of Recombinant Proteins In Milk

Since the introduction of the first exogenous genes into mice, more than 60 proteins have been produced in milk of transgenic animals. In order to target protein expression specifically to the mammary gland, a transgene typically consists of the desired protein gene fused to one of several available mammary-specific regulatory sequences.1-3-7-1 These sequences have included: ovine BLG; murine, rat, and rabbit whey acidic protein (WAP); bovine a-sj casein; rat, rabbit, and goat b-casein; and guinea pig, ovine and caprine, and bovine a-lactalbumin. While expression of the target protein can be achieved using either a genomic DNA or cDNA coding sequence(s), the former normally yields higher levels of protein expression.

Therapeutic monoclonal antibodies produced in the mammary gland of a transgenic animal line present a potentially valuable technology. Transgenic monoclonal antibodies are produced by cloning genetic sequences for both heavy- and light-chain genes downstream of mammary gland-specific regulatory elements. Chimeric antibodies may also be produced by ligating antigen-binding region sequences from a (usually murine) monoclonal antibody to constant region sequences from a different species and/or isotype. The first transgenic mice harboring immunoglobulin genes were made in the mid-1980s.[8] Though the majority of effort and funding in this field is currently focused toward human therapeutics, veterinary use of monoclonal antibodies also shows significant promise as a developing application.

Whereas several therapeutic monoclonal antibodies have been approved for use by the U.S. Food and Drug Administration, none as yet has been approved where a transgenic animal was used as a production vehicle. Using antibody production technologies in transgenic biore-actor systems, these products target a wide range of clinical ailments and are mostly in the preclinical stage of development.

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