nbsprotВестник войск РХБ защитыJournal of NBC Protection Corps2587-57283034-279127 Научный центр10.35825/2587-5728-2021-5-2-103-122tagreknbsprot-69Research ArticleБиологическая безопасность и защита от биологических угрозBiological Security and Protection against Biological ThreatsСинтетическая биология – друг или враг? Каких угроз нам следует ожидать?Synthetic Biology – Friend or Foe? What Kind of Threats Should We Expect?ЛакотаЯ.LakotaJ.

Ян Лакота. MD, PhD

Дубравская 9, 841 04, Братислава; ул. Бойцы Сопротивления 10, 820 05, Братислава

Ján Lakota. MD, PhD

Dubravská cesta 9, 841 04 Bratislava; Odbojárov 10, 820 05 Bratislava

jan.lakota@savba.skЦентр экспериментальной медицины, Академия наук Словакии; Факультет менеджмента, Университет им. Я.А. КоменскогоСловакияCentre of Experimental Medicine, SAS; Slovakia Faculty of Management Comenius UniversitySlovakia20210506202352103122Copyright © Лакота Я., 20232023Лакота Я.Lakota J.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nbsprot.ru/jour/article/view/69

Синтетическая биология – недавно появившаяся ветвь технологий двойного назначения, новая область применения инженерных принципов в биологии. Цель работы – показать основные технологические приемы этой технологии и привести конкретные примеры ее использования для создания новых видов биологических поражающих агентов и приемов ведения биологической войны, ранее немыслимых и представленных только в научно-фантастических книгах. Основные инструменты и методические приемы синтетической биологии: синтез и секвенирование больших фрагментов ДНК; разработка «платформы» («шасси») – т.е. системы-хозяина, несущей генетический набор инструментов для экспрессии желаемых генов сконструированного биологического пути, доставляемых подходящими векторами; разработка систем транскрипции, не истощающих ресурсы клетки (синтетические промоторы и факторы транскрипции); инструменты модификации генома (нуклеаза CRISPR/Cas9, нуклеазы цинковых пальцев, TALE нуклеазы, мегануклеазы); и компьютерные инструменты (участвующие в базовом структурном проектировании и синтезе; в проектировании сети; в прогнозировании поведения/функции/реакции). Синтетическая биология уже показала большие возможности в воссоздании известных патогенных вирусов и патогенных бактерий; в повышении опасности для людей существующих патогенных бактерий и вирусов (например, путем повышения их вирулентности или способности преодолевать иммунитет); создании патогенов, ранее не существовавших в природе; производства токсичных химикатов или биохимических веществ с использованием естественных и искусственных метаболических путей; изготовлении токсических веществ посредством синтеза in situ; изменение микробиома человека; изменения иммунной системы человека; модификации генома человека путем добавления, удаления или модификации генов или посредством эпигенетических изменений, которые изменяют экспрессию генов и могут передаваться от родителя к ребенку во время репродукции, распространяя генетические изменения в популяции. В работе подробно рассмотрены возможности синтетической биологии для разработки новых средств и способов ведения биологической войны. Например, введение в геном вируса эктромелии (оспы мышей) гена интерлейкина-4 значительно повысило его вирулентность для мышей. Он подавлял первичные иммунные ответы и преодолевал ранее существовавший иммунитет к исходному вирусу. Аналогичный результат был получен с рекомбинантным аденовирусом, кодирующим нейрональный токсин индийской змеи бунгаруса – бунгаротоксин. Путем введения в составе инъекционных препаратов антигенов, похожих на собственные белки человека, можно за короткий срок вызвать аутоиммунное состояние у тысяч людей, которое проявится у них через годы рассеянным склерозом и другими энцефалопатиями. Приводится работа, опубликованная в 2018 г., в которой утверждается, что современные технологии синтетической биологии и математического моделирования эпидемий, если уже известен иммунодоминантный эпитоп патогена, позволяют сконструировать такой его вариант, который при «столкновении» с наиболее вероятным иммунным ответом человека будет эволюционировать в сторону большей контагиозности и способности преодолевать иммунитет, сформировавшийся в результате уже перенесенной болезни или вакцинации. Автор считает, что необходимо не только постоянно отслеживать эти новые биотехнологии двойного назначения, но и совершенствовать традиционные и научные методы мониторинга их использования.

Synthetic biology is a newly emerging branch of dual-use technology. It is a combination of biology and different branches of engineering. The aim of this article is to show the main technological methods of synthetic biology and to give specific examples of its use to create new types of biological agents and methods of biological warfare, previously unthinkable and presented only in science fiction. Basic tools and techniques of synthetic biology are: DNA synthesis and DNA sequencing; «chassis», i.e. host system harboring the genetic toolbox for expression of the desired genes, delivered by suitable vectors, of the engineered biological pathway; engineering of transcription systems that do not deplete the resources of the cell (synthetic promotors and transcription factors); genome modification tools (CRISPR/Cas9 nuclease, zinc finger nucleases, TALE nucleases, meganucleases); computer-aided tools (involved in basic structural design and synthesis; in network design; in prediction of behavior/function/response). Synthetic biology has already demonstrared its capabilities in re-creating known pathogenic viruses and pathogenic bacteria; in making existing pathogenic bacteria and viruses more dangerous for humans; in creating new pathogens; in manufacturing toxic chemicals or biochemicals by exploiting natural and artificial metabolic pathways; in making toxic chemicals and biochemicals via in situ synthesis; in modifying the human microbiome; in modifying the human immune system; in modifying the human genome (through addition, deletion, or modification of genes or through epigenetic changes that modify gene expression and can pass from parent to child during reproduction and thus spread a genetic change through the population over time). The article discusses in detail the possibilities of synthetic biology for the development of new means of biological warfare. The author believes that it is necessary not only to constantly monitor these new dual-use biotechnologies, but also to improve traditional and scientific methods of their monitoring.

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The authors declare that there are no conflicts of interest present.