Interfering Nanoparticles for Silencing MicroRNAs
Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California, USA. Methods in enzymology
(Impact Factor: 2.09).
01/2012; 509:339-53. DOI: 10.1016/B978-0-12-391858-1.00017-4
MicroRNAs (miRNAs) are single-stranded noncoding RNAs ∼21-nucleotide (nt) in length and regulate gene expression at the posttranscriptional level. miRNAs are involved in almost every area of biology, including developmental processes, disease pathogenesis, and host-pathogen interactions. Dysregulation of miRNAs in various disease states makes them potential targets for therapeutic intervention. Specific miRNAs can be silenced by anti-microRNAs (anti-miRs) that are chemically modified antisense oligonucleotides complementary to mature miRNA sequences. In vivo delivery of anti-miRs is the main barrier in achieving efficient silencing of target miRNAs. A new systemic delivery agent, interfering nanoparticles (iNOPs), was designed and prepared from lipid-functionalized poly-L-lysine dendrimer. iNOPs can efficiently deliver small RNAs, including short interfering RNAs, miRNA mimics, and anti-miRs. Systemic delivery of a chemically stabilized anti-miR-122 by iNOPs effectively silences miR-122 in mouse liver. Intravenous administration of 2 mg/kg anti-miR-122 complexed with iNOP-7 results in 83% specific silencing of target miRNA. The specific silencing of miR-122 by iNOP-7 is long lasting and does not induce an immune response.
Available from: Xiong Ma
- "Intravenous administration of interfering nanoparticles (iNOPs), which are prepared by lipid-functionalized poly-L-lysine dendrimer, results in 83% specific silencing of target miRNA. The specific silencing of miR-122 by iNOP-7 is long-lasting and does not induce an immune response . Lipid-based nanoparticles (LNPs) containing oleic acid (OA), an unsaturated fatty acid, also demonstrate the delivery efficacy of miRNA and the inhibition of the target (Bcl-w) to a greater degree than with Lipofectamine 2000 . "
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ABSTRACT: Intrahepatic portal hypertension accounts for most of the morbidity and mortality encountered in patients with liver cirrhosis, due to increased portal inflow and intrahepatic vascular resistance. Most treatments have focused only on portal inflow or vascular resistance. However, miRNA multitarget regulation therapy may potentially intervene in these two processes for therapeutic benefit in cirrhosis and portal hypertension. This review presents an overview of the most recent knowledge of and future possibilities for the use of miRNA therapy. The benefits of this therapeutic modality-which is poorly applied in the clinical setting-are still uncertain. Increasing the knowledge and current understanding of the roles of miRNAs in the development of intrahepatic portal hypertension and hepatic stellate cells (HSCs) functions, as well as their potential as novel drug targets, is critical.
04/2014; 2014(12):797898. DOI:10.1155/2014/797898
Available from: Dimitry A Chistiakov
- "Systemic delivery of a chemically stabilized anti-miR-122 by iNOPs into a mouse liver resulted in a long-term inhibition of miR-122 by 83% and did not induce an immune response (Baigude & Rana, 2012). There are only a few reports for using nanoparticlemediated delivery of miRNAs in cardiovascular therapy. "
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ABSTRACT: Context: MicroRNAs (miRNAs) are important and powerful mediators in a variety of diseases including cardiovascular pathology. Thus, they emerged as interesting new drug targets. However, it is important to develop efficient transfer tools to successfully deliver miRNAs or antisense oligonucleotides (antagomirs) to the target tissue. Objective: The aim of this study was to review the scientific literature on delivery techniques currently used for transfer of miRNAs and antagomirs to animal models of cardiovascular disease and those that are likely to be used for therapeutic miRNA transport in the nearest future. Methods: The research was carried out by consulting the following medical websites: Medicus Medline Index, PubMed (National Library of Medicine), and a registry database of clinical trials conducted in USA ( www.clinicaltrials.gov ). The selection gathers articles written in English, published from January 2012. Results: A current delivery technique includes chemical modification of antagomirs with 2-O-methyl-group or 2-O-methyoxyethyl or using locked nucleic acids to increase drug stability and affinity. Development of miRNA sponges/decoys aims to target all members of a miRNA seed family of interest. A further strategy to augment miRNA levels is to use miRNA delivery through viral-based vectors including adenoviruses, adeno-associated viruses, and lentiviruses. To date, a variety of nanocarriers is available for efficient delivery of miRNAs. Microvesicles, and apoptotic bodies that contain circulating miRNAs could be also used as therapeutic transport systems in the nearest future. Conclusion: Development of new miRNA carrier systems with advanced properties and large animal data in the cardiovascular field is highly recommended.
Drug Delivery 11/2012; 19(8):392-405. DOI:10.3109/10717544.2012.738436 · 2.56 Impact Factor
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ABSTRACT: Prostate cancer is the most prevalent tumor in the male population and the second leading cause of cancer-related death in men in Western countries. Besides genetic and epigenetic aberrations in protein coding genes, alterations in microRNAs equally contribute to prostate cancer initiation and progression. In this context, a plethora of overwhelming evidence establishes the involvement of microRNAs as essential actors in the multi-step cascade fostering a prostate cancer cell to leave the primary tumor and form secondary tumors at distant sites. Herein, we describe how specific microRNAs may impinge on the different stages of prostate cancer metastasis and review published profiling studies in which microRNA expression data have been analyzed in relation to clinical parameters of progression for the identification of novel biomarkers. We also provide evidence concerning the possibility to manipulate metastasis-related microRNA functions, either by mimicking or inhibiting them, as a highly promising strategy for the development of innovative therapeutic approaches for the advanced disease.
Current Medicinal Chemistry 02/2013; 20(12). DOI:10.2174/0929867311320120007 · 3.85 Impact Factor
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