vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestib-331Research ArticleОБЗОРЫREVIEWSCpG-ОЛИГОДЕЗОКСИНУКЛЕОТИДЫ И ИХ ПРАКТИЧЕСКОЕ ПРИМЕНЕНИЕCpG OLIGODEOXYNUCLEOTIDES AND THEIR PRACTICAL USAGEЗинченкоА. И.ZinchenkoA. I.

член-корреспондент, д-р биол. наук, профессор, заведующий лабораторией

ул. Купревича, 2, 220141

Corresponding Member, D. Sc. (Biol.), Professor, Head of the Laboratory

2, Kuprevich Str., 220141

zinch@mbio.bas-net.byЩеколоваА. С.ShchokolovaA. S.

канд. биол. наук, ст. науч. сотрудник

ул. Купревича, 2, 220141

Ph. D. (Biol.), Senior researcher

2, Kuprevich Str., 220141

nastindeathnote@gmail.comИнститут микробиологии НАН Беларуси, МинскInstitute of Microbiology of the National Academy of Sciences of Belarus, Minsk2017161220170496106Copyright © Зинченко А.И., Щеколова А.С., 20172017Зинченко А.И., Щеколова А.С.Zinchenko A.I., Shchokolova A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/331

Бактериальные ДНК (в том числе плазмиды) и синтетические олиго-2ʹ-дезоксинуклеотиды, содержащие неметилированные CpG-динуклеотиды (CpG-ОДН), при введении в организм человека и животных стимулируют как врожденные, так и адаптивные иммунные ответы. В связи с этим терапевтическое применение CpG-ОДН против инфекционных, онкологических и аллергических заболеваний является весьма перспективным. Однако молекулы CpG-ОДН заряжены отрицательно и поэтому с трудом проникают через клеточные мембраны, имеющие аналогичный поверхностный заряд. Кроме того, природные CpG-ОДН легко расщепляются нуклеазами. Одним из эффективных способов защиты CpG-ОДН от деградации нуклеазами является химическая модификация их сахарофосфатного скелета. В то же время известны случаи, когда введение таких модифицированных молекул приводило к серьезным побочным эффектам. Все эти обстоятельства существенно ограничивают терапевтическое применение CpG-ОДН и подогревают интерес к поиску эффективных систем доставки CpG-ОДН в ткани и клетки-мишени.

Наблюдаемый в последние годы существенный прогресс в области нанобиотехнологий предоставил беспрецедентные возможности для инкапсулирования лекарственных субстанций (в том числе CpG-ОДН) в различные наноразмерные транспортные системы, а также для синтеза из CpG-ОДН разнообразных по форме наноразмерных структур. При использовании таких систем доставки значительно повышается как стабильность CpG-ОДН, так и степень их интернализации в клетки-мишени. Кроме того, применение таких транспортных наносистем, возможно, позволит отказаться от вызывающей побочные эффекты химической модификации CpG-ОДН. 

Bacterial DNA (including plasmids) and synthetic oligo-2ʹ-deoxynucleotides containing non-methylated CpGdinucleotides (CpG-ODN) upon introduction into human or animal body stimulate both innate and adaptive immune responses. In this regard bright prospects open up for therapeutic application of CpG-ODN to cope with infectious, allergic diseases and cancer. However, CpG-ODN molecules are negatively charged and hence can hardly penetrate through cell membrane bearing the equipolar surface charge. Moreover, native CpG-ODN are easily cleaved by nucleases. One of the effective methods to counter CpG-ODN nuclease attack is chemical modification of their sugar-phosphate skeleton. Yet some cases have been reported when supply of modified molecules caused grave side-effects. All these circumstances restrain considerably therapeutic prospects of CpG-ODN and spur-up the interest in search of efficient systems for CpG-ODN delivery to target tissues and cells. Lately progress of nanobiotechnologies provided unprecedented opportunities for encapsulation of active drug substances (including CpG-ODN) into various nanosize transport vehicles and synthesis of multiform nanostructures from CpG-ODN. The use of such delivery systems raises significantly both CpG-ODN stability and extent of their internalization into target cells. It is plausible that development of nanotransporters will enable to get rid of chemical CpG-ODN modification provoking adverse effects. 

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