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It uses cellular machinery and small, designed RNAs in the form of synthetic small interfering RNAs (siRNAs) or vector\u2010based short hairpin RNAs (shRNAs), and artificial miRNAs (amiRNAs) to inhibit a gene of interest. Artificial miRNAs, known also as miRNA mimics, shRNA\u2010miRs, or pri\u2010miRNA\u2010like shRNAs have the most complex structures and undergo two\u2010step processing in cells to form mature siRNAs, which are RNAi effectors. AmiRNAs are composed of a target\u2010specific siRNA insert and scaffold based on a natural primary miRNA (pri\u2010miRNA). siRNAs serve as a guide to search for complementary sequences in transcripts, whereas pri\u2010miRNA scaffolds ensure proper processing and transport. The dynamics of siRNA maturation and siRNA levels in the cell resemble those of endogenous miRNAs; therefore amiRNAs are safer than other RNAi triggers. Delivered as viral vectors and expressed under tissue\u2010specific polymerase II (Pol II) promoters, amiRNAs provide long\u2010lasting silencing and expression in selected tissues. Therefore, amiRNAs are useful therapeutic tools for a broad spectrum of human diseases, including neurodegenerative diseases, cancers and viral infections. Recent reports on the role of sequence and structure in pri\u2010miRNA processing may contribute to the improvement of the amiRNA tools. In addition, the success of a recently initiated clinical trial for Huntington's disease could pave the way for other amiRNA\u2010based therapies, if proven effective and safe.<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>RNA Processing &gt; Processing of Small RNAs<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Regulatory RNAs\/RNAi\/Riboswitches &gt; RNAi: Mechanisms of Action<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA in Disease and Development &gt; RNA in Disease<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.1640","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T02:51:17Z","timestamp":1609555877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Artificial <scp>miRNAs<\/scp> as therapeutic tools: Challenges and opportunities"],"prefix":"10.1002","volume":"12","author":[{"given":"Anna","family":"Kotowska\u2010Zimmer","sequence":"first","affiliation":[{"name":"Department of Genome Engineering Institute of Bioorganic Chemistry PAS  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9298-1955","authenticated-orcid":false,"given":"Marianna","family":"Pewinska","sequence":"additional","affiliation":[{"name":"Department of Genome Engineering Institute of Bioorganic Chemistry PAS  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-6302","authenticated-orcid":false,"given":"Marta","family":"Olejniczak","sequence":"additional","affiliation":[{"name":"Department of Genome Engineering Institute of Bioorganic Chemistry PAS  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2008.147"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki567"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.15.9556-9565.2005"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0051-6"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.01.031"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.03.051"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.006"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2008.123"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv219"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.07.144"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2015.122"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau6414"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.231"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.17"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.1062908"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87885"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.03.015"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00696-y"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.7135204"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2015.043"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9635-3_13"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth923"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09092"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1645"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1725"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022437"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03868"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.205"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl143"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e318258b60a"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00008-08"},{"key":"e_1_2_14_34_1","article-title":"Journey to the center of the cell: Tracing the path of AAV transduction","author":"Dhungel B. 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