10 September 2013

Transgenic goats will help in the treatment of cancer

Russian scientists have raised a transgenic goat for tumor therapy

Svetlana Yastrebova, InformnaukaBiotechnologies, an indisputable breakthrough in the history of civilization, can and should be improved.


The first substances obtained using biotechnologies were extracted from simple organisms, such as bacteria. However, bacteria, for all their attractive simplicity of structure and breeding, are very far from humans, and often the proteins obtained with their help do not quite correspond to the desired ones. Mammals are much more convenient in this sense, because in their cells the protein synthesis system is similar to that of humans.

Currently, work is underway to create transgenic animals capable of producing the required hormones, enzymes or other proteins. Scientists from Novosibirsk, together with Brazilian colleagues, obtained transgenic goats capable of producing a protein that stimulates hematopoiesis in the bone marrow, which is important in the rehabilitation of cancer patients after removal of tumors. The animals are completely healthy and secrete a large amount of the required protein with milk.


An animal that can ensure the future of thousands of cancer patients

When mentioning the term "transgenic animal", mice come to mind more often than goats. Indeed, there are already a great many different lines of mice with artificially altered DNA, but almost all of them are used in scientific research and bring rather new information, but not commercial benefits. Keeping a herd of ungulates in the laboratory (and most laboratory animals participate in only one series of experiments during their lives) is a dubious and expensive pleasure. But it is much more convenient to breed transgenic goats for commercial purposes than mice: you can make sure that the animal will secrete the necessary protein with milk, and the yield from the goat is quite significant, which cannot be said about small rodents.

Russian scientists started working with transgenic goats more than ten years ago, when they raised an animal that gives milk with human lactoferrin. This time, another group of scientists from Brazil and the Russian Institute of Molecular Genetics of the Russian Academy of Sciences and the Laboratory of Developmental Genetics of the Institute of Cytology and Genetics of the SB RAS set out to create goats that produce human granulocyte-colony stimulating factor (G-CSF).

Transgenic goats were obtained in Brazil on the basis of the Faculty of Goat and Sheep Breeding at the University of Ceara by direct injection of DNA of a genetically engineered structure into the pronucleus (analogous to the nucleus) of fertilized eggs. Subsequently, these eggs were transplanted to the recipient hormone-stimulated goats. DNA injections into the pronucleus are currently the only way to obtain transgenic animals.

This protein stimulates the work of the bone marrow, an organ that produces new blood cells and the immune system. Such stimulation is sometimes needed by patients who have undergone surgery to remove a malignant tumor. When the latter is cut out, bone marrow cells are transplanted to the patient, which need to be "forced" to work in order to restore immunity and blood composition. Thanks to therapy with G-CSF, bone marrow cells quickly recover in number, and in less than a month, hematopoiesis completely returns to normal. The colony-stimulating factor can be administered both with radiation sickness and with other hematopoietic disorders.

The only drawback of this method of treatment is its high cost. A full course of G-CSF therapy now costs 6000-12000 US dollars. As the study showed, the use of transgenic goats can significantly reduce these costs.

Oleg Serov, Head of the Laboratory of Developmental Genetics at the Institute of Cytology and Genetics SB RAS, explains: "Simple calculations show that if a transgenic goat secretes human G-CSF into milk at the level of 1 mg/ml (or 1 gram per liter), with an average milk yield of 200-300 liters per lactation period, 200-300 grams of the desired squirrel. Of course, when G-CSF is isolated from milk, there will be losses of up to 70%, but at the output from a liter of milk, at least 300 mg of the drug can be expected. Therapeutic doses of G-CSF are from 5 to 10 mg per full course. It follows from this that a herd of transgenic goats of 25-30 heads is able to provide from 5,000 to 9,000 liters per year, which potentially provides production of 1.5-9 kilograms of G-CSF, that is, covers the needs of millions of patients."

A group of Brazilian and Russian scientists have raised two transgenic animals, a male and a female, they are healthy and give offspring. The study revealed that all clinical indicators of goats are normal, and the required protein is contained only in the milk of the animal, but not in its blood (the latter could have a bad effect on the health of the goat and would mean that the expression of the gene does not go as planned). Previous experiments on obtaining animals secreting granulocyte colony stimulating factor were conducted on transgenic mice at the Institute of Cytology and Genetics SB RAS in Novosibirsk. Here, all the necessary genetic engineering structures were tested on rodents.

Now that the method of obtaining transgenic animals that secrete G-CSF has been worked out, it is possible to put the production of protein on an industrial, commercial basis. Scientists do not have specific agreements with biotech companies yet, but I want to believe that everything is still ahead and such a promising project will find practical implementation, the benefits of which real patients will be able to evaluate.

Source of information: Moura et al., Dynamics of recombinant hG-CSF in transgenic goat: preliminary study in the founder during hormonally induced lactation. Animal Biotechnology, 24, 2013, 10-14.

Portal "Eternal youth" http://vechnayamolodost.ru10.09.2013

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