<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vestib</journal-id><journal-title-group><journal-title xml:lang="ru">Известия Национальной  академии наук Беларуси. Серия биологических наук</journal-title><trans-title-group xml:lang="en"><trans-title>Proceedings of the National Academy of Sciences of Belarus, Biological Series</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1029-8940</issn><issn pub-type="epub">2524-230X</issn><publisher><publisher-name>The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29235/1029-8940-2018-63-2-232-244</article-id><article-id custom-type="elpub" pub-id-type="custom">vestib-367</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>МАЛЫЕ НЕКОДИРУЮЩИЕ РНК: БИОЛОГИЧЕСКАЯ РОЛЬ И БИОМЕДИЦИНСКОЕ ПРИМЕНЕНИЕ</article-title><trans-title-group xml:lang="en"><trans-title>SMALL NON-CODING RNA: BIOLOGICAL FUNCTIONS AND BIOMEDICAL APPLICATION</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Абашкин</surname><given-names>В. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Abashkin</surname><given-names>V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>мл. науч. сотрудник</p></bio><bio xml:lang="en"><p>Junior researcher</p></bio><email xlink:type="simple">victor.abashkin@yandex.by</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дмитрук</surname><given-names>О. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Dzmitruk</surname><given-names>V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>канд. биол. наук, ст. науч. сотрудник</p></bio><bio xml:lang="en"><p>Ph. D. (Biol.), Senior researcher</p></bio><email xlink:type="simple">dmitruk.olga@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Щербин</surname><given-names>Д. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Shcharbin</surname><given-names>D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д-р биол. наук, доцент, заведующий лабораторией</p></bio><bio xml:lang="en"><p>D. Sc. (Biol.), Assistant Professor, Head of the Laboratory</p></bio><email xlink:type="simple">d.shcharbin@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Институт биофизики и клеточной инженерии НАН Беларуси, Минск</institution></aff><aff xml:lang="en"><institution>Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus,&#13;
Minsk</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>21</day><month>05</month><year>2018</year></pub-date><volume>63</volume><issue>2</issue><fpage>232</fpage><lpage>244</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Абашкин В.М., Дмитрук О.Г., Щербин Д.Г., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Абашкин В.М., Дмитрук О.Г., Щербин Д.Г.</copyright-holder><copyright-holder xml:lang="en">Abashkin V., Dzmitruk V., Shcharbin D.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vestibio.belnauka.by/jour/article/view/367">https://vestibio.belnauka.by/jour/article/view/367</self-uri><abstract><p>Малые некодирующие РНК (мнРНК) – короткие РНК, участвующие в регуляции экспрессии генов, иммунитете клетки и посттранскрипционных модификациях РНК. Среди всего разнообразия мнРНК наибольший интерес в плане биомедицинского применения представляют три класса малых РНК: малые интерферирующие РНК (миРНК), микроРНК и piwi-interacting РНК (пиРНК). МиРНК и микроРНК схожи по функциям и механизму действия: их главной задачей является сайленсинг генов на посттранскрипционном этапе. В отличие от них, пиРНК обеспечивает, главным образом, стабильность генома эмбриона путем блокирования активности мобильных элементов ДНК. Дисрегуляция мнРНК наблюдается при различных заболеваниях. Установлено, что нарушения экспрессии мнРНК возникают при развитии онкологических, неврологических, сердечно-сосудистых заболеваний, диабете. МнРНК могут выступать в качестве диагностических биомаркеров заболеваний и как компонент генно-терапевтических препаратов. Использование мнРНК как биомаркеров в медицине весьма перспективно, а существующие ограничения связаны со сложностью выявления мнРНК, различающихся одним или несколькими нуклеотидами. Весьма многообещающим является использование мнРНК в генной терапии, поскольку с их помощью гипотетически возможно отключить любой белковый компонент, не изменяя геном, что гораздо безопаснее других предлагаемых методов генной терапии. Главной задачей для клинического использования миРНК и микроРНК на сегодняшний день является создание эффективных систем доставки в клетки-мишени, поскольку несвязанные мнРНК не способны проникать через мембраны и разрушаются под действием ряда ферментов крови и тканей. Таким образом, несмотря на ряд имеющихся проблем, мнРНК являются перспективными агентами для диагностики и терапии целого спектра заболеваний.</p></abstract><trans-abstract xml:lang="en"><p>Small non-coding RNAs (sncRNA) are short RNA molecules that are involved in gene expression, posttranscriptional modifications and cell immunity regulation. The most studied and the most interesting for the medical application classes are small interfering RNA (siRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). SncRNAs have a wide range of functions. Primary function of siRNA and miRNA is silencing of gene expression by binding or/and degradation of messenger RNA. PiRNA also have this function but its principal function is control of genome stability on the basis of blocking the activity of transposons. Many diseases, such as cancer, diabetes, neurological, and cardiovascular diseases are accompanied by distortion of sncRNA expression. Abnormal sncRNA expression profile can be used as a hallmark to determine certain type of cancer. In all types of cancer were discovered deviations in the sncRNA pool. From the medical point of view sncRNA can be used as disease marker or as a component of gene therapeutic drugs. In the case of markers usage sncRNAs deserve attention as universal and relatively stable samples. But frequently sncRNAs differ just by few nucleotides, which can create difficulties in their distinguishing. In the frame of gene therapy sncRNAs are able to silence theoretically any gene expression. As sncRNA affects mRNA but not DNA it allows avoiding accidental changes in the genome. In this case delivery systems for RNAs are highly needed, because sncRNAs are unable to penetrate the cell membrane and can be degraded by blood enzymes. Despite of existing problems, sncRNAs are promising compounds for the diagnosis and therapy of wide range of diseases.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>миРНК</kwd><kwd>микроРНК</kwd><kwd>пиРНК</kwd><kwd>генная терапия</kwd><kwd>терапия рака</kwd></kwd-group><kwd-group xml:lang="en"><kwd>ncRNA</kwd><kwd>siRNA</kwd><kwd>miRNA</kwd><kwd>piRNA</kwd><kwd>gene therapy</kwd><kwd>cancer treatment</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа поддержана Белорусским республиканским фондом фундаментальных исследований (гранты Б15РМ-60, Б16-071, М15СО-041).</funding-statement><funding-statement xml:lang="en">This work was supported by grants Belarusian Republican Foundation for Fundamental Research (B15RM-60, B16-071, М15СО-041)</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Cech, T. R. The noncoding RNA revolution-trashing old rules to forge new ones / T. R. Cech, J. A. Steitz // Cell. – 2014. – Vol. 157, N 1. – P. 77–94.</mixed-citation><mixed-citation xml:lang="en">Cech T. R., Steitz J. A. The noncoding RNA revolution-trashing old rules to forge new ones. Cell, 2014, vol. 157, no. 1, pp. 77–94. DOI: 10.1016/j.cell.2014.03.008</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Aravin, A. Identiﬁcation and characterization of small RNAs involved in RNA silencing / A. Aravin, T. Tuschl // FEBS Letters. – 2005. – Vol. 579, N 26. – P. 5830–5840.</mixed-citation><mixed-citation xml:lang="en">Aravin A., Tuschl T. Identiﬁcation and characterization of small RNAs involved in RNA silencing. FEBS Letters, 2005, vol. 579, no. 26, pp. 5830–5840. DOI: 10.1016/j.febslet.2005.08.009</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Systematic analysis of small RNAs associated with human mitochondria by deep sequencing: detailed analysis of mitochondrial associated miRNA / L. Spirada [et al.] // PloS One. – 2012. – Vol. 7, N 9. – P. e44873.</mixed-citation><mixed-citation xml:lang="en">Sripada L., Tomar D., Prajapati P., Singh R., Singh A. K., Singh R. Systematic analysis of small RNAs associated with human mitochondria by deep sequencing: detailed analysis of mitochondrial associated miRNA. PloS One, 2012, vol. 7, no. 9, pp. e44873. DOI: 10.1371/journal.pone.0044873</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Comparative analysis of the small RNA transcriptomes of Pinus contorta and Oryza sativa / R. D. Morin [et al.] // Genome Research. – 2008. – Vol. 18, N 4. – P. 571–584.</mixed-citation><mixed-citation xml:lang="en">Morin R. D., Aksay G., Dolgosheina E., Ebhardt H. A., Magrini V., Mardis E. R., Sahinalp S. C., Unrau P. J. Comparative analysis of the small RNA transcriptomes of Pinus contorta and Oryza sativa. Genome Research, 2008, vol. 18, no. 4, pp. 571–584. DOI: 10.1101/gr.6897308</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">A small chloroplast RNA may be required for trans-splicing in Chlamydomonas reinhardtii / M. Goldschmidt-Clermont [et al.] // Cell. – 1991. – Vol. 65, N 1. – P. 135–143.</mixed-citation><mixed-citation xml:lang="en">Goldschmidt-Clermont M., Choquet Y., Girard-Bascou J., Michel F., Schirmer-Rahire M., Rochaix J. D. A small chlo- roplast RNA may be required for trans-splicing in Chlamydomonas reinhardtii. Cell, 1991, vol. 65, no. 1, pp. 135–143. DOI: 10.1016/0092-8674(91)90415-u</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Majdalani, N. Bacterial small RNA regulators / N. Majdalani, C. K. Vanderpool, S. Gottesman // Critical Reviews in Biochemistry and Molecular Biology. – 2005. – Vol. 40, N 2. – P. 93–113.</mixed-citation><mixed-citation xml:lang="en">Majdalani N., Vanderpool C. K., Gottesman S. Bacterial small RNA regulators. Critical Reviews in Biochemistry and Molecular Biology, 2005, vol. 40, no. 2, pp. 93–113. DOI: 10.1080/10409230590918702</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Hussain, M. MicroRNA-like viral small RNA from Dengue virus 2 autoregulates its replication in mosquito cells / M. Hussain, S. Asgari // Proc. of the Nat. Acad. of Sciences. – 2014. – Vol. 111, N 7. – P. 2746–2751.</mixed-citation><mixed-citation xml:lang="en">Hussain M., Asgari S. MicroRNA-like viral small RNA from Dengue virus 2 autoregulates its replication in mosquito cells. Proceedings of the National Academy of Sciences, 2014, vol. 111, no. 7, pp. 2746–2751. DOI: 10.1073/pnas.1320123111</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Hamilton, A. J. A species of small antisense RNA in posttranscriptional gene silencing in plants / A. J. Hamilton, D. Baulcombe // Science. – 1999. – Vol. 286, N 5441. – P. 950–952.</mixed-citation><mixed-citation xml:lang="en">Hamilton A. J., Baulcombe D. C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science, 1999, vol. 286, no. 5441, pp. 950–952. DOI: 10.1126/science.286.5441.950</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes / T. Watanabe [et al.] // Nature. – 2008. – Vol. 453, N 7194. – P. 539–543.</mixed-citation><mixed-citation xml:lang="en">Watanabe T., Totoki Y., Toyoda A., Kaneda M., Kuramochi-Miyagawa S., Obata Y., Chiba H., Kohara Y., Kono T., Nakano T., Surani M. A., Sakaki Y., Sasaki H. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature, 2008, vol. 453, no. 7194, pp. 539–543. DOI: 10.1038/nature06908</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Yang, N. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells /</mixed-citation><mixed-citation xml:lang="en">Yang N., Kazazian H. H. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nature Structural &amp; Molecular Biology, 2006, vol. 13, no. 9, pp. 763–771. DOI: 10.1038/nsmb1141</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">N. Yang, H. H. Kazazian // Nature Structural &amp; Molecular Biology. – 2006. – Vol. 13, N 9. – P. 763–771.</mixed-citation><mixed-citation xml:lang="en">Mello C. C., Conte D. Revealing the world of RNA interference. Nature, 2004, vol. 431, no. 7006, pp. 338–342. DOI: 10.1038/nature02872</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Mello, C. C. Revealing the world of RNA interference / C. C. Mello, D. Conte // Nature. – 2004. – Vol. 431, N 7006. – P. 338–342.</mixed-citation><mixed-citation xml:lang="en">Ghildiyal M., Seitz H., Horwich M. D., Li C., Du T., Lee S., Xu J., Kittler E. L. W., Zapp M. L., Weng Z. Zamore P. D. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science, 2008, vol. 320, no. 5879, pp. 1077–1081. DOI: 10.1126/science.1157396</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells / M. Ghildiyal [et al.] // Science. – 2008. – Vol. 320, N 5879. – P. 1077–1081.</mixed-citation><mixed-citation xml:lang="en">Cao W., Hunter R., Strnatka D., McQueen C. A., Erickson R. P. DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response. Journal of Applied Genetics, 2005, vol. 46, no. 2, pp. 217–225.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response / W. Cao [et al.] // J. of Applied Genetics. – 2005. – Vol. 46, N 2. – P. 217–225.</mixed-citation><mixed-citation xml:lang="en">Yi R., Qin Y., Macara I. G., Cullen B. R. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes and Development, 2003, vol. 17, no. 24, pp. 3011–3016. DOI: 10.1101/gad.1158803</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs / R. Yi [et al.] // Genes and Development. – 2003. – Vol. 17, N 24. – P. 3011–3016.</mixed-citation><mixed-citation xml:lang="en">Saito K., Siomi M. C. Small RNA-mediated quiescence of transposable elements in animals. Developmental Cell, 2010, vol. 19, no. 5, pp. 687–697. DOI: 10.1016/j.devcel.2010.10.011</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Saito, K. Small RNA-mediated quiescence of transposable elements in animals / K. Saito, M. C. Siomi // Developmental Cell. – 2010. – Vol. 19, N 5. – P. 687–697.</mixed-citation><mixed-citation xml:lang="en">Wang H. W., Noland C., Siridechadilok B., Taylor D. W., Ma E., Felderer K., Doudna J. A., Nogales E. Structural insights into RNA processing by the human RISC-loading complex. Nature Structural and Molecular Biology, 2009, vol. 16, no. 11, pp. 1148–1153. DOI: 10.1038/nsmb.1673</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Structural insights into RNA processing by the human RISC-loading complex / H. W. Wang [et al.] // Nature Structural and Molecular Biology. – 2009. – Vol. 16, N 11. – P. 1148–1153.</mixed-citation><mixed-citation xml:lang="en">Bernstein E., Caudy A. A., Hammond S. M., Hannon G. J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 2001, vol. 409, no. 6818, pp. 363–366. DOI: 10.1038/35053110</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Role for a bidentate ribonuclease in the initiation step of RNA interference / E. Bernstein [et al.] // Nature. – 2001. – Vol. 409, N 6818. – P. 363–366.</mixed-citation><mixed-citation xml:lang="en">Brummelkamp T. R., Bernards R., Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science, 2002, vol. 296, no. 5567, pp. 550–553. DOI: 10.1126/science.1068999</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Brummelkamp, T. R. A system for stable expression of short interfering RNAs in mammalian cells / T. R. Brummelkamp, R. Bernards, R. Agami // Science. – 2002. – Vol. 296, N 5567. – P. 550–553.</mixed-citation><mixed-citation xml:lang="en">Janowski B. A., Younger S. T., Hardy D. B., Ram R., Huffman K. E., Corey D. R. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nature Chemical Biology, 2007, vol. 3, no. 3, pp. 166–173. DOI: 10.1038/ nchembio860</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Activating gene expression in mammalian cells with promoter-targeted duplex RNAs / B. A. Janowski [et al.] // Nature Chemical Biology. – 2007. – Vol. 3, N 3. – P. 166–173.</mixed-citation><mixed-citation xml:lang="en">Janowski B. A., Huffman K. E., Schwartz J. C., Ram R., Hardy D., Shames D. S., Minna J. D., Corey D. R. Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs. Nature Chemical Biology, 2005, vol. 1, no. 4, p. 216–222. DOI: 10.1038/nchembio725</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs / B. A. Janowski [et al.] // Nature Chemical Biology. – 2005. – Vol. 1, N 4. – P. 216–222.</mixed-citation><mixed-citation xml:lang="en">Squadrito M. L., Baer C., Burdet F., Maderna C., Gilﬁllan G. D., Lyle R., Ibberson M., De Palma M. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Reports, 2014, vol. 8, no. 5, pp. 1432–1446. DOI: 10.1016/j.celrep.2014.07.035</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells / M. L. Squadrito [et al.] // Cell Reports. – 2014. – Vol. 8, N 5. – P. 1432–1446.</mixed-citation><mixed-citation xml:lang="en">Wienholds E., Plasterk R. H. A. MicroRNA function in animal development. FEBS Letters, 2005, vol. 579, no. 26, pp. 5911–5922. DOI: 10.1016/j.febslet.2005.07.070</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Wienholds, E. MicroRNA function in animal development / E. Wienholds, R. H. A. Plasterk // FEBS Letters. – 2005. – Vol. 579, N 26. – P. 5911–5922.</mixed-citation><mixed-citation xml:lang="en">Kim Y. K., Kim V. N. Processing of intronic microRNAs. EMBO Journal, 2007, vol. 26, no. 3, pp. 775–783. DOI: 10.1038/sj.emboj.7601512</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Kim, Y. K. Processing of intronic microRNAs / Y. K. Kim, V. N. Kim // EMBO Journal. – 2007. – Vol. 26, N 3. – P. 775–783.</mixed-citation><mixed-citation xml:lang="en">Cai X., Hagedorn C. H., Cullen B. R. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA, 2004, vol. 10, no. 12, pp. 1957–1966. DOI: 10.1261/rna.7135204</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Cai, X. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs / X. Cai, C. H. Hagedorn, B. R. Cullen // RNA. – 2004. – Vol. 10, N 12. – P. 1957–1966.</mixed-citation><mixed-citation xml:lang="en">Borchert G. M., Lanier W., Davidson B. L. RNA polymerase III transcribes human microRNAs. Nature Structural and Molecular Biology, 2006, vol. 13, no. 12, pp. 1097–1101. DOI: 10.1038/nsmb1167</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Borchert, G. M. RNA polymerase III transcribes human microRNAs / G. M. Borchert, W. Lanier, B. L. Davidson // Nature Structural and Molecular Biology. – 2006. – Vol. 13, N 12. – P. 1097–1101.</mixed-citation><mixed-citation xml:lang="en">Han J., Lee Y., Yeom K. H., Nam J. W., Heo I., Rhee J. K., Sohn S. Y., Cho Y., Zhang B. T., Kim V. N. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell, 2006, vol. 125, no. 5, pp. 887–901. DOI: 10.1016/j. cell.2006.03.043</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex / J. Han [et al.] // Cell. – 2006. – Vol. 125, N 5. – P. 887–901.</mixed-citation><mixed-citation xml:lang="en">Brennecke J., Aravin A. A., Stark A., Dus M., Kellis M., Sachidanandam R., Hannon G. J. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell, 2007, vol. 128, no. 6, pp. 1089–1103. DOI: 10.1016/j.cell.2007.01.043</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila / J. Brennecke [et al.] // Cell. – 2007. – Vol. 128, N 6. – P. 1089–1103.</mixed-citation><mixed-citation xml:lang="en">Juliano C., Wang J., Lin H. Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annual Review of Genetics, 2011, vol. 45, no. 1, pp. 447–469. DOI: 10.1146/annurev-genet-110410-132541</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Juliano, C. Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms / C. Juliano, J. Wang, H. Lin // Annu. Rev. of Genetics. – 2011. – Vol. 45, N 1. – P. 447–469.</mixed-citation><mixed-citation xml:lang="en">Hartig J. V., Tomari Y., Förstemann K. piRNAs – the ancient hunters of genome invaders. Genes and Development, 2007, vol. 21, no. 14, pp. 1707–1713. DOI: 10.1101/gad.1567007</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Hartig, J. V. piRNAs – the ancient hunters of genome invaders / J. V. Hartig, Y. Tomari, K. Förstemann // Genes and Development. – 2007. – Vol. 21, N 14. – P. 1707–1713.</mixed-citation><mixed-citation xml:lang="en">Ishizu H., Siomi H., Siomi M. C. Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines. Genes and Development, 2012, vol. 26, no. 21, pp. 2361–2373. DOI: 10.1101/gad.203786.112</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Ishizu, H. Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines / H. Ishizu, H. Siomi, M. C. Siomi // Genes and Development. – 2012. – Vol. 26, N 21. – P. 2361–2373.</mixed-citation><mixed-citation xml:lang="en">Watanabe T., Chuma S., Yamamoto Y., Kuramochi-Miyagawa S., Totoki Y., Toyoda A., Hoki Y., Fujiyama A., Shibata T., Sado T., Noce T., Nakano T., Nakatsuji N., Lin H., Sasaki H. MITOPLD is a mitochondrial protein essential for nuage formation devcel.2011.01.005</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline / T. Watanabe [et al.] // Developmental Cell. – 2011. – Vol. 20, N 3. – P. 364–375.</mixed-citation><mixed-citation xml:lang="en">Nishimasu H., Ishizu H., Saito K., Fukuhara S., Kamatani M. K., Bonnefond L., Matsumoto N., Nishizawa T., Nakanaga K., Aoki J., Ishitani R., Siomi H., Siomi M. C., Nureki O. Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature, 2012, vol. 491, no. 7423, pp. 284–287. DOI: 10.1038/nature11509</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Structure and function of Zucchini endoribonuclease in piRNA biogenesis / H. Nishimasu [et al.] // Nature. – 2012. – Vol. 491, N 7423. – P. 284–287.</mixed-citation><mixed-citation xml:lang="en">Mohn F., Handler D., Brennecke J. piRNA-guided slicing speciﬁes transcripts for Zucchini-dependent, phased piRNA biogenesis. Science, 2015, vol. 348, no. 6236, pp. 812–817. DOI: 10.1126/science.aaa1039</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Mohn, F. piRNA-guided slicing speciﬁes transcripts for Zucchini-dependent, phased piRNA biogenesis / F. Mohn, D. Handler, J. Brennecke // Science. – 2015. – Vol. 348, N 6236. – P. 812–817.</mixed-citation><mixed-citation xml:lang="en">Izumi N., Shoji K., Sakaguchi Y., Honda S., Kirino Y., Suzuki T., Katsuma S., Tomari, Y. Identiﬁcation and functional analysis of the pre-piRNA 3′ Trimmer in silkworms. Cell, 2016, vol. 164, no. 5, pp. 962–973. DOI: 10.1016/j.cell.2016.01.008</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Identiﬁcation and functional analysis of the pre-piRNA 3′ Trimmer in silkworms / N. Izumi [et al.] // Cell. – 2016. – Vol. 164, N 5. – P. 962–973.</mixed-citation><mixed-citation xml:lang="en">Saito K., Sakaguchi Y., Suzuki T., Suzuki T., Siomi H., Siomi M. C. Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi-interacting RNAs at their 3′ ends. Genes and Development, 2007, vol. 21, no. 13, pp. 1603–1608. DOI: 10.1101/gad.1563607</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi-interacting RNAs at their 3′ ends / K. Saito [et al.] // Genes and Development. – 2007. – Vol. 21, N 13. – P. 1603–1608.</mixed-citation><mixed-citation xml:lang="en">Fedyanin M. Yu., Ignatova E. O., Tyulyandin S. A. MicroRNA role in solid tumors. Zlokachestvennye opukholi [Malignant Tumours], 2013, no. 1 (5), pp. 3–14 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Федянин, М. Ю. Роль микро-РНК при солидных опухолях / М. Ю. Федянин, Е. О. Игнатова, С. А. Тюляндин // Злокачеств. опухоли. – 2013. – № 1 (5). – С. 3–14.</mixed-citation><mixed-citation xml:lang="en">Cheng J., Deng H., Xiao B., Zhou H., Zhou F., Shen Z., Guo J. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Letters, 2012, vol. 315, no. 1, pp. 12–17. DOI: 10.1016/j.canlet.2011.10.004</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells / J. Cheng [et al.] // Cancer Letters. – 2012. – Vol. 315, N 1. – P. 12–17.</mixed-citation><mixed-citation xml:lang="en">Chen R. X., Xia Y. H., Xue T. C., Ye S. L. Suppression of microRNA-96 expression inhibits the invasion of hepatocellular carcinoma cells. Molecular Medicine Reports, 2012, vol. 5, no. 3, pp. 800–804. DOI: 10.3892/mmr.2011.695</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Suppression of microRNA-96 expression inhibits the invasion of hepatocellular carcinoma cells / R. X. Chen [et al.] // Molecular Medicine Reports. – 2012. – Vol. 5, N 3. – P. 800–804.</mixed-citation><mixed-citation xml:lang="en">Moon J., Xu L., Giffard R. G. Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss. Journal of Cerebral Blood Flow and Metabolism, 2013, vol. 33, no. 12, pp. 1976–1982. DOI: 10.1038/jcbfm.2013.157</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Moon, J. Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss / J. Moon, L. Xu, R. G. Giffard // J. of Cerebral Blood Flow and Metabolism. – 2013. – Vol. 33, N 12. – P. 1976–1982.</mixed-citation><mixed-citation xml:lang="en">Krichevsky A. M., Gabriely G. miR 21: a small multi ‐faceted RNA. Journal of Cellular and Molecular Medicine, 2009, vol. 13, no. 1, pp. 39–53. DOI: 10.1111/j.1582-4934.2008.00556.x</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Krichevsky, A. M. miR 21: a small multi ‐ faceted RNA / A. M. Krichevsky, G. Gabriely // J. of Cellular and Molecular Medicine. – 2009. – Vol. 13, N 1. – P. 39–53.</mixed-citation><mixed-citation xml:lang="en">Cheng J., Guo J. M., Xiao B. X., Miao Y., Jiang Z., Zhou H., Li Q. N. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clinica Chimica Acta, 2011, vol. 412, no. 17–18, pp. 1621–1625. DOI: 10.1016/j.cca.2011.05.015</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells / J. Cheng [et al.] // Clinica Chimica Acta. – 2011. – Vol. 412, N 17–18. – P. 1621–1625.</mixed-citation><mixed-citation xml:lang="en">Merritt W. M., Lin Y. G., Han L. Y., Kamat A. A., Spannuth W. A., Schmandt R., Urbauer D., Pennacchio L. A., Cheng J. F., Nick A. M., Deavers M. T., Mourad-Zeidan A., Wang H., Mueller P., Lenburg M. E., Gray J. W., Mok S., Birrer M. J., Lopez-Berestein G., Coleman R. L., Bar-Eli M., Sood A. K. Dicer, Drosha, and outcomes in patients with ovarian cancer. New England Journal of Medicine, 2008, vol. 359, no. 25, pp. 2641–2650. DOI: 10.1056/nejmoa0803785</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Dicer, Drosha, and outcomes in patients with ovarian cancer / W. M. Merritt [et al.] // New England J. of Medicine. – 2008. – Vol. 359, N 25. – P. 2641–2650.</mixed-citation><mixed-citation xml:lang="en">Hébert S. S., Papadopoulou A. S., Smith P., Galas M. C., Planel E., Silahtaroglu A. N., Sergeant N., Buée L., De Strooper B. Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Human Molecular Genetics, 2010, vol. 19, no. 20, pp. 3959–3969. DOI: 10.1093/hmg/ddq311</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration / S. S. Hébert [et al.] // Human Molecular Genetics. – 2010. – Vol. 19, N 20. – P. 3959–3969.</mixed-citation><mixed-citation xml:lang="en">Haramati S., Chapnik E., Sztainberg Y., Eilam R., Zwang R., Gershoni N., McGlinn E., Heiser P. W., Wills A. M., Wirguin I, Rubin L. L., Misawa H., Tabin C. J., Brown Jr. R., Chen A., Hornstein E. miRNA malfunction causes spinal motor neuron disease Proceedings of the National Academy of Sciences, 2010, vol. 107, no. 29, pp. 13111–13116. DOI: 10.1073/ pnas.1006151107</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">miRNA malfunction causes spinal motor neuron disease / S. Haramati [et al.] // Proc. of the Nat. Acad. of Sciences. – 2010. – Vol. 107, N 29. – P. 13111–13116.</mixed-citation><mixed-citation xml:lang="en">Fang Y., Shi C., Manduchi E., Civelek M., Davies P. F. MicroRNA-10a regulation of proinﬂammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proceedings of the National Academy of Sciences, 2010, vol. 107, no. 30, pp. 13450–13455. DOI: 10.1073/pnas.1002120107</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">MicroRNA-10a regulation of proinﬂammatory phenotype in athero-susceptible endothelium in vivo and in vitro / Y. Fang [et al.] // Proc. of the Nat. Acad. of Sciences. – 2010. – Vol. 107, N 30. – P. 13450–13455.</mixed-citation><mixed-citation xml:lang="en">Kong L., Zhu J., Han W., Jiang X., Xu M., Zhao Y., Dong Q., Pang Z., Guan Q., Gao L., Zhao J., Zhao L. Signiﬁcance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetologica, 2011, vol. 48, no. 1, pp. 61–69. DOI: 10.1007/s00592-010-0226-0</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Signiﬁcance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study / L. Kong [et al.] // Acta Diabetologica. – 2011. – Vol. 48, N 1. – P. 61–69.</mixed-citation><mixed-citation xml:lang="en">Ji L., Chen X. Regulation of small RNA stability: methylation and beyond. Cell Research, 2012, vol. 22, no. 4, pp. 624– 636. DOI: 10.1038/cr.2012.36</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Ji, L. Regulation of small RNA stability: methylation and beyond / L. Ji, X. Chen // Cell Research. – 2012. – Vol. 22, N 4. – P. 624–636.</mixed-citation><mixed-citation xml:lang="en">Davies B. P., Arenz C. A ﬂuorescence probe for assaying micro RNA maturation. Bioorganic and Medicinal Chemistry, 2008, vol. 16, no. 1, pp. 49–55. DOI: 10.1016/j.bmc.2007.04.055</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Davies, B. P. A ﬂuorescence probe for assaying micro RNA maturation / B. P. Davies, C. Arenz // Bioorganic and Medicinal Chemistry. – 2008. – Vol. 16, N 1. – P. 49–55.</mixed-citation><mixed-citation xml:lang="en">Mattie M. D., Benz C. C., Bowers J., Sensinger K., Wong L., Scott G. K., Fedele V., Ginzinger D., Getts R., Haqq C. Optimized high-throughput microRNA expression proﬁling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Molecular Cancer, 2006, vol. 5, no. 1. 14 p. DOI: 10.1186/1476-4598-5-24</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Optimized high-throughput microRNA expression proﬁling provides novel biomarker assessment of clinical prostate and breast cancer biopsies / M. D. Mattie [et al.] // Molecular Cancer. – 2006. – Vol. 5, N 1. –14 p.</mixed-citation><mixed-citation xml:lang="en">Grimm D., Streetz K. L., Jopling C. L., Storm T. A., Pandey K., Davis C. R., Marion P., Salazar F., Kay M. A. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature, 2006, vol. 441, no. 7092, pp. 537–541. DOI: 10.1038/nature04791</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways / D. Grimm [et al.] // Nature. – 2006. – Vol. 441, N 7092. – P. 537–541.</mixed-citation><mixed-citation xml:lang="en">Aagaard L., Rossi J. J. RNAi therapeutics: principles, prospects and challenges. Advanced Drug Delivery Reviews, 2007, vol. 59, no. 2–3, pp. 75–86. DOI: 10.1016/j.addr.2007.03.005</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Aagaard, L. RNAi therapeutics: principles, prospects and challenges / L. Aagaard, J. J. Rossi // Advanced Drug Delivery Reviews. – 2007. – Vol. 59, N 2–3. – P. 75–86.</mixed-citation><mixed-citation xml:lang="en">Judge A. D., Bola G., Lee A. C., MacLachlan I. Design of noninﬂammatory synthetic siRNA mediating potent gene silencing in vivo. Molecular Therapy, 2006, vol. 13, no. 3, pp. 494–505. DOI: 10.1016/j.ymthe.2005.11.002</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Design of noninﬂammatory synthetic siRNA mediating potent gene silencing in vivo / A. D. Judge [et al.] // Molecular Therapy. – 2006. – Vol. 13, N 3. – P. 494–505.</mixed-citation><mixed-citation xml:lang="en">Laganà A., Acunzo M., Romano G., Pulvirenti A., Veneziano D., Cascione L., Giugno R., Gasparini P., Shasha D., Ferro A., Croce C. M. miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs. Nucleic Acids Research, 2014, vol. 42, no. 9, pp. 5416–5425. DOI: 10.1093/nar/gku202</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs / A. Laganà [et al.] // Nucleic Acids Research. – 2014. – Vol. 42, N 9. – P. 5416–5425.</mixed-citation><mixed-citation xml:lang="en">Bader A. G., Brown D., Winkler M. The promise of microRNA replacement therapy. Cancer Research, 2010, vol. 70, no. 18, pp. 7027–7030. DOI: 10.1158/0008-5472.can-10-2010</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Bader, A. G. The promise of microRNA replacement therapy / A. G. Bader, D. Brown, M. Winkler // Cancer Research. – 2010. – Vol. 70, N 18. – P. 7027–7030.</mixed-citation><mixed-citation xml:lang="en">Ishida M., Selaru F. M. miRNA-based therapeutic strategies. Current Pathobiology Reports, 2013, vol. 1, no. 1, pp. 63–70. DOI: 10.1007/s40139-012-0004-5</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Ishida, M. miRNA-based therapeutic strategies / M. Ishida, F. M. Selaru // Current Pathobiology Reports. – 2013. – Vol. 1, N 1. – P. 63–70.</mixed-citation><mixed-citation xml:lang="en">Krützfeldt J., Kuwajima S., Braich R., Rajeev K. G., Pena J., Tuschl T., Manoharan M., Stoffel M. Speciﬁcity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Research, 2007, vol. 35, no. 9, pp. 2885–2892. DOI: 10.1093/nar/gkm024</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Speciﬁcity, duplex degradation and subcellular localization of antagomirs / J. Krützfeldt [et al.] // Nucleic Acids Research. – 2007. – Vol. 35, N 9. – P. 2885–2892.</mixed-citation><mixed-citation xml:lang="en">Huang J. B., Liang J., Zhao X. F., Wu W. S., Zhang F. Epigenetics: novel mechanism of pulmonary hypertension. Lung, 2013, vol. 191, no. 6, pp. 601–610. DOI: 10.1007/s00408-013-9505-1</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Epigenetics: novel mechanism of pulmonary hypertension / J. B. Huang [et al.] // Lung. – 2013. – Vol. 191, N 6. – P. 601–610.</mixed-citation><mixed-citation xml:lang="en">Sun H. X., Zeng D. Y., Li R. T., Pang R. P., Yang H., Hu Y. L., Zhang Q., Jiang Y., Huang L. Y., Tang Y. B., Yan G. J., Zhou J. G. Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension, 2012, vol. 60, no. 6, pp. 1407–1414. DOI: 10.1161/hypertensionaha.112.197301</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase / H. X. Sun [et al.] // Hypertension. – 2012. – Vol. 60, N 6. – P. 1407–1414.</mixed-citation><mixed-citation xml:lang="en">Esteller M. Cancer epigenomics: DNA methylomes and histone-modiﬁcation maps. Nature Reviews Genetics, 2007, vol. 8, no. 4, pp. 286–298. DOI: 10.1038/nrg2005</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Esteller, M. Cancer epigenomics: DNA methylomes and histone-modiﬁcation maps / M. Esteller // Nature Reviews Genetics. – 2007. – Vol. 8, N 4. – P. 286–298.</mixed-citation><mixed-citation xml:lang="en">Whitehead K. A., Langer R., Anderson D. G. Knocking down barriers: advances in siRNA delivery. Nature Reviews Drug Discovery, 2009, vol. 8, no. 2, pp. 129–138. DOI: 10.1038/nrd2742</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Whitehead, K. A. Knocking down barriers: advances in siRNA delivery / K. A. Whitehead, R. Langer, D. G. Anderson // Nature Reviews Drug Discovery. – 2009. – Vol. 8, N 2. – P. 129–138.</mixed-citation><mixed-citation xml:lang="en">Gary D. J., Puri N., Won Y. Y. Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery. Journal of Controlled Release, 2007, vol. 121, no. 1, pp. 64–73. DOI: 10.1016/j. jconrel.2007.05.021</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Gary, D. J. Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery / D. J. Gary, N. Puri, Y. Y. Won // J. of Controlled Release. – 2007. – Vol. 121, N 1. – P. 64–73.</mixed-citation><mixed-citation xml:lang="en">Pereira D. M., Rodrigues P. M., Borralho P. M., Rodrigues C. M. Delivering the promise of miRNA cancer therapeutics. Drug Discovery Today, 2013, vol. 18, no. 5–6, pp. 282–289. DOI: 10.1016/j.drudis.2012.10.002</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Delivering the promise of miRNA cancer therapeutics / D. M. Pereira [et al.] // Drug Discovery Today. – 2013. – Vol. 18, N 5–6. – P. 282–289.</mixed-citation><mixed-citation xml:lang="en">Weber N., Ortega P., Clemente M. I., Shcharbin D., Bryszewska M., de la Mata F. J., Gómez R., Muñoz-Fernández M. A. Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes. Journal of Controlled Release, 2008, vol. 132, no. 1, pp. 55–64. DOI: 10.1016/j.jconrel.2008.07.035</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes / N. Weber [et al.] // J. of Controlled Release. – 2008. – Vol. 132, N 1. – P. 55–64.</mixed-citation><mixed-citation xml:lang="en">Ionov M., Ciepluch K., Garaiova Z., Melikishvili S., Michlewska S., Balcerzak Ł., Glińska S., Miłowska K., Gomez-Ramirez R., de la Mata F. J., Shcharbin D., Waczulikova I., Bryszewska M., Hianik T. Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid monolayers. Biochimica et Biophysica Acta (BBA) – Biomembranes, 2015, vol. 1848, no. 4, pp. 907–915. DOI: 10.1016/j.bbamem.2014.12.025</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid monolayers / M. Ionov [et al.] // Biochimica et Biophysica Acta (BBA) – Biomembranes. – 2015. – Vol. 1848, N 4. – P. 907–915.</mixed-citation><mixed-citation xml:lang="en">Ionov M., Lazniewska J., Dzmitruk V., Halets I., Loznikova S., Novopashina D., Apartsin E., Krasheninina O., Venyaminova A., Milowska K., Nowacka O., Gomez-Ramirez R., de la Mata F. J., Majoral J. P., Shcharbin D., Bryszewska M. Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction. International Journal of Pharmaceutics, 2015, vol. 485, no. 1–2, pp. 261–269. DOI: 10.1016/j.ijpharm.2015.03.024</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction / M. Ionov [et al.] // Intern. J. of Pharmaceutics. – 2015. – Vol. 485, N 1–2. – P. 261–269.</mixed-citation><mixed-citation xml:lang="en">Dzmitruk V., Szulc A., Shcharbin D., Janaszewska A., Shcharbina N., Lazniewska J., Novopashina D., Buyanova M., Ionov M., Klajnert-Maculewicz B., Gómez-Ramirez R., Mignani S., Majoral J. P., Muñoz-Fernández M. A., Bryszewska M. Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efﬁciency of pharmacological action. International Journal of Pharmaceutics, 2015, vol. 485, no. 1–2, pp. 288–294. DOI: 10.1016/j.ijpharm.2015.03.034</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efﬁciency of pharmacological action / V. Dzmitruk [et al.] // Intern. J. of Pharmaceutics. – 2015. – Vol. 485, N 1–2. – P. 288–294.</mixed-citation><mixed-citation xml:lang="en">Ihnatsyeu-Kachan A., Dzmitruk V., Apartsin E., Krasheninina O., Ionov M., Loznikova S., Venyaminova A., Miłowska K., Shcharbin D., Mignani S., Muñoz-Fernández M. A., Majoral J. P., Bryszewska M. Multi-target inhibition of cancer cell growth by SiRNA cocktails and 5-ﬂuorouracil using effective piperidine-terminated phosphorus dendrimers. Colloids and Interfaces, 2017, vol. 1, no. 1. 18 p. DOI: 10.3390/colloids1010006</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Multi-target inhibition of cancer cell growth by SiRNA cocktails and 5-ﬂuorouracil using effective piperidine-terminated phosphorus dendrimers / A. Ihnatsyeu-Kachan [et al.] // Colloids and Interfaces. – 2017. – Vol. 1, N 1. – 18 P.</mixed-citation><mixed-citation xml:lang="en">Titze-de-Almeida R., David C., Titze-de-Almeida S. S. The Race of 10 Synthetic RNAi-based drugs to the pharmaceutical market. Pharmaceutical Research, 2017, vol. 34, no. 7, pp. 1339–1363. DOI: 10.1007/s11095-017-2134-2</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Titze-de-Almeida, R. The race of 10 synthetic RNAi-based drugs to the pharmaceutical market / R. Titze-de-Almeida, C. David, S. S. Titze-de-Almeida // Pharmaceutical Research. – 2017. – Vol. 34, N 7. – P. 1339–1363.</mixed-citation><mixed-citation xml:lang="en">Pearson S., Jia H., Kandachi K. China approves ﬁrst gene therapy. Nature Biotechnology, 2004, vol. 22, pp. 3–4. DOI: 10.1038/nbt0104-3</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Pearson, S. China approves ﬁrst gene therapy / S. Pearson, H. Jia, K. Kandachi // Nature Biotechnology. – 2004. – Vol. 22. – P. 3–4.</mixed-citation><mixed-citation xml:lang="en">Valdmanis P. N., Lisowski L., Kay M. A. rAAV-mediated tumorigenesis: still unresolved after an AAV assault. Molecular Therapy, 2012, vol. 20, no. 11, pp. 2014–2017. DOI: 10.1038/mt.2012.220</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Valdmanis, P. N. rAAV-mediated tumorigenesis: still unresolved after an AAV assault / P. N. Valdmanis, L. Lisowski, M. A. Kay // Molecular Therapy. – 2012. – Vol. 20, N 11. – P. 2014–2017.</mixed-citation><mixed-citation xml:lang="en">Booth C., Gaspar H. B., Thrasher A. J. Treating immunodeﬁciency through HSC gene therapy. Trends in Molecular Medicine, 2016, vol. 22, no. 4, pp. 317–327. DOI: 10.1016/j.molmed.2016.02.002</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Booth, C. Treating immunodeﬁciency through HSC gene therapy / C. Booth, H. B. Gaspar, A. J. Thrasher // Trends in Molecular Medicine. – 2016. – Vol. 22, N 4. – P. 317–327.</mixed-citation><mixed-citation xml:lang="en">FDA approval brings ﬁrst gene therapy to the United States. CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia. U. S. Food and Drug Administration. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm574058.htm (accessed 13.12.2017).</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">FDA approval brings ﬁrst gene therapy to the United States. CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia [Electronic resource] // U.S. Food and Drug Administration. – Mode of access: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm574058.htm. – Date of access: 13.12.2017.</mixed-citation><mixed-citation xml:lang="en">FDA approval brings ﬁrst gene therapy to the United States. CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia [Electronic resource] // U.S. Food and Drug Administration. – Mode of access: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm574058.htm. – Date of access: 13.12.2017.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
