Биоминерализация геномной ДНК человека в цеолитоподобный металлоорганический каркасный полимер ZIF-8

И.Х. Шайхутдинов, П.В. Ильясов, Л.В. Лимарева, А.С. Сустретов, Д.А. Кокорев, А.В. Соколов

Ключевые слова: биоминерализация; инкапсуляция; металлоорганические каркасные полимеры; геномная ДНК человека; генетические векторы; полимер ZIF-8.

2024, том 16, номер 1, стр. 5.

DOI: https://doi.org/10.17691/stm2024.16.1.01

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Аннотация
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Цель исследования — оценить возможности биоминерализации геномной ДНК человека в металлоорганический каркасный полимер (МОКП) ZIF-8 и сохранения включенной последовательности ДНК после цикла инкапсуляции и растворения композита. Данное исследование является начальным этапом разработки абиотического вектора для работы с нативными нуклеиновыми кислотами произвольного размера на основе композита ДНК@ZIF-8.

Материалы и методы. Объектом исследования послужила геномная ДНК человека, выделенная из лимфоцитов периферической крови здоровых добровольцев, с использованием набора «Проба-НК» (НПО «ДНК-Технология», Россия). Оценку чистоты и концентрации геномной ДНК проводили спектрофотометрически при длинах волн 260/280 нм на планшет-ридере Tecan Infinity 200 Pro (Tecan Instruments, Австрия). Синтез ZIF-8 выполняли в физиологических условиях (37°С) путем смешивания водных растворов солей цинка с 2-метилимидазолом при различных мольных соотношениях. В аналогичных условиях была проведена биоминерализация геномной ДНК человека в ZIF-8. Полученный МОКП и композит ДНК@ZIF-8 исследовали методом порошковой рентгеновской дифрактометрии на дифрактометре Phaser D2 (Bruker, США), удельную площадь поверхности оценивали на порозиметре Autosorb iQ (Quantachrome, США). Для количественной оценки инкапсулированной ДНК композит ДНК@ZIF-8 растворяли в цитратном буфере. Сохранность ДНК определяли методом аллель-специфической ПЦР в режиме реального времени (АС-ПЦР) с использованием наборов для исследования однонуклеотидных полиморфизмов (НПФ «Литех», Россия) на амплификаторе Quantstudio 6 Pro (Thermo Scientific, США). В случае использования наборов с электрофоретической детекцией амплификацию проводили на термоциклере T100 (Thermo Scientific, США).

Результаты. Получены полимер ZIF-8 и композит ДНК@ZIF-8 при различных мольных соотношениях ионов цинка с 2-метилимидазолом, охарактеризована их структура и удельная площадь поверхности. Определена эффективность биоминерализации геномной ДНК, которая составила порядка 7–8%. ПЦР-анализ биоминерализованной ДНК показал сохранность неселективно выбранных локусов.

Заключение. В результате исследований подтверждена возможность инкапсуляции геномной ДНК в металлоорганический каркасный полимер ZIF-8. ДНК после биоминерализации сохраняет пригодность для использования в исследованиях по формированию и изучению генетических конструктов.

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