ORIGINAL RESEARCH

Distribution of intravenously injected small interfering RNAs in organs and tissues

Kuzevanova AYu1, Luneva AS2, Maslov MA2, Karpukhin AV1, Alimov AA
About authors

1 Laboratory of Molecular Genetics of Complexly Inherited Diseases,
Research Centre of Medical Genetics, Moscow, Russia

2 Preobrazhensky Department of Chemistry and Technology of Bioactive Compounds,
Institute of Fine Chemical Technologies, Moscow, Russia

Correspondence should be addressed: Andrei Alimov
ul. Moskvorechie, d. 1, Moscow, Russia, 115478; ur.xednay@0102vomila.ierdna

About paper

Acknowledgements: authors thank Olga Konyaeva and Natalia Kulbachevskaya of Blokhin Russian Cancer Research Center for providing consultations and technical assistance with the animals.

Contribution of the authors to this work: Kuzevanova AYu — analysis of literature, data collection, analysis, and interpretation; Luneva AS — preparation of liposomes; Maslov MA — research planning, preparation of liposomes; Karpukhin AV — analysis of literature, research planning, data interpretation, drafting of a manuscript; Alimov AA — analysis of literature, research planning, data collection, analysis and interpretation, drafting of a manuscript. All authors participated in editing of the manuscript.

Received: 2017-06-20 Accepted: 2017-06-24 Published online: 2017-07-19
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There are a number of problems that need to be addressed when designing an effective RNA interference-based drug including distribution of intravenously injected exogenous small interfering RNAs (siRNAs) in the organs and tissues of the patient. Insufficient data on siRNA distribution obtained using isotopic/fluorescent labeling offers no insight into whether the polymer retains its original structure after the injection. Quantitative real-time polymerase chain reaction that we used in our work provides a better response to the challenge. In our experiment LIVIN–specific siRNAs injected intravenously were distributed unevenly between tissues and their accumulation was dose-dependent (the study was conducted in mice using 2.5 and 7.5 mg/kg doses). Maximal accumulation was observed in the liver and spleen where siRNA concentration continued to increase between 48 and 96 hours after its administration. This demonstrates that the studied cationic lisosome/miRNA complex has long circulation time. We believe that the obtained data will be instrumental in finding an effective therapeutic dose, designing adequate regimens and preparing for preclinical or clinical trials of siRNA-based drugs.

Keywords: small interfering RNA, cationic liposomes, mice, tissues, quantitative polymerase chain reaction

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