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Animals engineered with pinpoint accuracy

More accurate genetic modification has created allergen-free cow's milk and pigs that could serve as a model for atherosclerosis. 

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A cow in New Zealand has been genetically modified to produce hypoallergenic milk.

AgResearch

Two genetically engineered farm animals reported today illustrate how far from Frankenstein’s stitched-together monster animal biotechnology has come. One of those animals, a cow, secretes milk that lacks an allergy-inducing protein because researchers accurately blocked its production using the technique of RNA interference1. And in pigs, scientists have used an enzyme called a TALEN2 to scramble a gene that would normally help remove cholesterol.

RNA interference (RNAi) and TALENs are more accurate at targeting the gene in question than are earlier genetic engineering techniques. For years, researchers tried to remove the allergy-inducing milk protein beta-lactoglobulin from cow's milk, which can cause diarrhea and vomiting in some toddlers. They tried replacing the gene encoding beta-lactoglobulin with a defective form, but this proved nearly impossible because the techniques available to introduce foreign genes into animal genomes were not precise, and misplaced genes failed to express themselves correctly.

In 2006, scientists at AgResearch in Hamilton, New Zealand began to experiment with molecules that interfere with the messenger RNA go-between that enables translation of a gene into protein. In mice, they discovered a short chunk of RNA, called a microRNA, that targeted beta-lactoglobulin messenger RNA directly to prevent its translation. They inserted DNA encoding a version of this microRNA into the genome to create genetically modified cow embryos that they hoped would grow into cows without the allergen in their milk. Out of 100 embryos, one calf yielded beta-globulin-free milk. “This isn’t a quick process,” says Stefan Wagner, a molecular biologist at AgResearch. That's why it has taken so long to succeed in making an allergen-free cow, he says. 

Precision engineering

Wagner says that TALENs, which were not readily available when he began his research, might speed up the process, and that the team plans to use them to eliminate beta-lactoglobulin. RNAi cannot eliminate the protein completely because some messenger RNA slips past the blockade, but each TALEN targets a specific DNA sequence in the genome and cuts it. As the body repairs the break, mutations are often introduced that render the targeted gene non-functional. “The TALEN technology is staggeringly easy, quick, and leaves no mark in the genome,” says Bruce Whitelaw, a molecular biologist at the Roslin Institute near Edinburgh in the United Kingdom, who contributed to the work in pigs. “In essence, we are just mimicking an evolutionary process with precise, man-made editors.”

His team used TALENs to disrupt genes encoding low-density lipoprotein (LDL) receptors. Without these receptor proteins to remove cholesterol-containing LDLs from the blood, LDLs build-up and lead to atherosclerosis. Pigs with this condition may be reliable models of human atheroscelerosis in biomedical research.

The TALEN-modified pig is not the first model of human heart disease (see ‘Model pigs face a messy path’), but the technique makes genetic engineering less costly and more efficient. “I’d be exaggerating if I said that pigs and cows can now be thought of as big mice, but we are moving in that direction,” says Heiner Niemann, a bioengineer at the Institute of Farm Animal Genetics in Neustadt, Germany.

The excitement surrounding these technological advances is bittersweet, however. Originally, engineered animals were produced with the aim of making food safer, healthier and more abundant. Yet despite years of investment, almost no animal has been approved by regulatory agencies around the world. Wagner says he has not tasted the milk from his special cow because he’s not permitted to under New Zealand law. “We must restrict our research to scientific analysis,” he says. “The current climate for animal biotech is not very good, and therefore, we are nowhere near getting this to the consumer."

Journal name:
Nature
DOI:
doi:10.1038/nature.2012.11506

References

  1. Jabed, A. et al. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1210057109 (2012)

  2. Carlson, D. F. et al. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1211446109 (2012)

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  1. Avatar for Tommy Reagan
    Tommy Reagan

    The prohibition against mixing diverse animals or planting 2 types of seeds together under un-controlled conditions might be practical advice 2000 years ago given the state of science at that time, simply to prevent cross pollinating of two distinctive types of grain, for instance, to keep them from losing their distinctive qualities. It could have been a prohibition against mixing sheep with goats or other species that would result in neutered and therefore non-productive offspring. Some types of animals can combine like that but they produce sterile offspring.
    Regards, Tommy

  2. Avatar for Hana Johnson
    Hana Johnson

    Iâ&#x80&#x99m just wondering if this is store-bought soy milk or homemade. The reason why I ask is because I was under the impression that soy milk does not naturally contain calcium. I believe calcium is added to packaged soy milk. Could you confirm which brand of soy milk is being compared here?

  3. Avatar for Hana Johnson
    Hana Johnson

    But scientists at AgResearch in Hamilton, New Zealand, worked with molecules that interfere with messenger RNA (mRNA), which helps translate genes into proteins. They found microRNA (miRNA) in mice that targeted beta-lactoglobulin mRNA, so they inserted DNA encoding a version of this miRNA into the genomes of cow embryos. Out of 100 embryos, one calf produced beta-globulin-free milk. â&#x80&#x9cThis isnâ&#x80&#x99t a quick process,â&#x80&#x9d Stefan Wagner, a molecular biologist at AgResearch, told Nature. One problem I that RNA interference canâ&#x80&#x99t eliminate the protein completely because some mRNA slips through.

  4. Avatar for Hana Johnson
    Hana Johnson

    Robert MacLaren, a consultant opthalmic surgeon at the Moorfields Eye Hospital in London, and Robin Ali, a professor of human molecular genetics at UCLâ&#x80&#x99s Institute of Opthalmology, led research in which photoreceptor progenitor cells from embryonic rats were transplanted into the retinae of adult animals engineered to have non-functional photoreceptors. The cells used in the experiments are stem cells which do not retain the ability to differentiate into any cell type but are at a later, post-mitotic stage (i.e. they have stopped dividing).

    Three weeks after transplantation, examination of the host retinae showed that significant numbers of the cells â&#x80&#x93 up to 3,000 in each eye â&#x80&#x93 had migrated to the appropriate layer of the host retina, where they had integrated into the retinal tissue, differentiated into photoreceptors and formed functional synapses with other cells (below). The transplanted cells partially restored the sensitivity of the mice to light, as measured by recordings of the electrical activity of the cells in response to light shone in the animalsâ&#x80&#x99 eyes.

  5. Avatar for Craig Campbell
    Craig Campbell

    Leviticus 19:19 also states... "Do not wear clothing woven from two different kinds of thread". I Do you think that means we have to all stop wearing poly-cotton shirts? The prohibition against mixing diverse animals or planting 2 types of seeds together under un-controlled conditions might be practical advice 2000 years ago given the state of science at that time, simply to prevent cross pollinating of two distinctive types of grain, for instance, to keep them from losing their distinctive qualities. It could have been a prohibition against mixing sheep with goats or other species that would result in neutered and therefore non-productive offspring. Some types of animals can combine like that but they produce sterile offspring. I don't believe that was an absolute prohibition against genetic science if it is beneficial to humanity although of course genetic modifications must be carefully done and tested to prevent harmful defects from arising.

  6. Avatar for Mart Mart
    Mart Mart

    Leviticus 19:19
    New International Version (NIV)
    19 ââ&#x82¬Å&#x93ââ&#x82¬Ë&#x9cKeep my decrees.
    ââ&#x82¬Å&#x93ââ&#x82¬Ë&#x9cDo not mate different kinds of animals.
    ââ&#x82¬Å&#x93ââ&#x82¬Ë&#x9cDo not plant your field with two kinds of seed.

    In other words God tells us not to mix the species, the first such mix was the fallen angels and women creating the wicked half breeds who were wiped out by the flood, these half breeds infect human kind as evil spirits/demons as their bodies were wiped out in the flood.

    2 Peter 2
    New International Version (NIV)
    4 For if God did not spare angels when they sinned, but sent them to hell,[a] putting them in chains of darkness to be held for judgment; 5 if he did not spare the ancient world when he brought the flood on its ungodly people, but protected Noah, a preacher of righteousness, and seven others;

    Matthew 24:37
    New International Version (NIV)
    37 As it was in the days of Noah, so it will be at the coming of the Son of Man.

    At the end times these things are said to happen again, how much misery are these created creatues going to bring to the living plants/animal/humans remains to be but one thing that is true and that is the demons have polluted and destroyed many people so that they are only fit for hell!

  7. Avatar for David Tyler
    David Tyler

    It is worth being up-front about all the issues related to GM. In this particular case, the research paper has this paragraph (in the discussion):
    "In contrast to our mouse model in which we did not observe any obvious phenotypic anomalies, a phenotype was observed in the transgenic calf, which was born without a tail. Taillessness in cattle is a rare congenital abnormality, and has been previously reported as a phenotype in a transgenic calf produced from a microinjected, cloned embryo. A similar tail phenotype was observed in a cloned mouse and was shown to be caused by a mutation in this individual donor cell that was below the detection limit for chromosomal abnormalities and unmasked by cloning. Thus, it appears unlikely that the tailless phenotype of the calf is correlated with the transgene insertion, but rather with an unrelated mutation present in the donor cell used for NT. Further characterization of this transgenic cattle line will be required to clarify the cause for the taillessness in the miRNA 6-4 calf."
    That last sentence is important. It is probably wise not to start campaigning for commercialisation until anomalies like this are clarified.

  8. Avatar for Michael Chisnall
    Michael Chisnall

    Here in New Zealand the fruitloops are already out. One well-known anti-GE campaigner has come out complaining that the hypoallergenic cow resulted from "manipulating its lifeforce"!

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