Всероссийский научно-исследовательский институт физиологии, биохимии и питания животных – филиал Федерального государственного бюджетного научного учреждения «Федеральный научный центр животноводства – ВИЖ имени академика Л.К. Эрнста»

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Beta-lactoglobulin gene: from old technologies of transgenesis to new methods of genome editing: a review

Trubitsina T.P., Ryabykh V.P., Koloskova E.M., Yezersky V.A., Maksimenko S.V.

Institute of Animal Physiology, Biochemistry and Nutrition, Borovsk,

Kaluga Region, Russian Federation

Номер: No 3
Страницы: 15-34

Журнал: Problemy biologii productivnykh zhivotnykh - Problems of Productive Animal Biology

Ключевые слова:

genome editing, hybrid gene constructs, production of recombinant proteins with milk, site-specific nuclease, β-lactoglobulin gene

Аннотация:

ABSTRACT. In studies conducted in the world to aimed to create the animal producers of biologically active proteins with milk (the mammary gland as a bioreactor), a significant proportion belongs to work with the β-lactoglobulin gene (BLG). The review deals with the use of gene constructs involving BLG fragments at different stages of development of this research area. The idea of obtaining knockout animals on this gene attracted more than one generation of geneticists, since β-lactoglobulin protein for many consumers, especially as a component of baby food, is the main allergen of goat and cow's milk. The evolution and effectiveness of ways to achieve this goal are described, including the use of new technologies that allow the site-specific integration of the transgene, including the use of site-specific nucleases-ZFN (zinc-finger nucleases), TALEN (transcription activator-like effector nuclease) and CRISPR/Cas9 (clustered with reciprocated short palindromic repeats). In these new technologies, a site-specific double-stranded DNA rupture is obtained; damage is eliminated by a non-homologous joining of the ends or by repair by homologous recombination using DNA template (transgene) flanked by the arms of homology to the adjacent regions of the DNA target. The recovery process often leads to targeted mutations in the form of deletions or insertions of nucleotides, which can lead to mutations in the frame shift and gene knockout. CRISPR/Cas9 technology has become dominant in the creation of transgenic farm animals, making it possible to produce large genetically modified animals in a shorter time, mainly by micro-injection in zygotic pronuclei. The review focuses on the use of BLG fragments as part of hybrid genetic constructs. Among the new important applications of new technologies is the production of animals, which express monoclonal antibodies, β-interferon, lactoferrin, G-CSF and human lactoferrin in milk. In Russia, an embargo on the cultivation and breeding of genetically modified plants and animals for food production was introduced. However, if some version of the "easing" of this ban, in the light of obvious progress in genetic editing technologies, will not be adopted in the short term, the need to obtain animals that produce biologically active proteins of diagnostic and therapeutic use remains relevant.

Литература:

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