CpG-ОЛИГОДЕЗОКСИНУКЛЕОТИДЫ И ИХ ПРАКТИЧЕСКОЕ ПРИМЕНЕНИЕ

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. 

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