Interfering nanoparticles for silencing microRNAs.
ABSTRACT 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.
- SourceAvailable from: Dimitry A Chistiakov
[Show abstract] [Hide abstract]
- "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. "
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 · 2.20 Impact Factor
Article: Gene regulation by non-coding RNAs[Show abstract] [Hide abstract]
ABSTRACT: Abstract The past two decades have seen an explosion in research on non-coding RNAs and their physiological and pathological functions. Several classes of small (20-30 nucleotides) and long (>200 nucleotides) non-coding RNAs have been firmly established as key regulators of gene expression in myriad processes ranging from embryonic development to innate immunity. In this review, we focus on our current understanding of the molecular mechanisms underlying the biogenesis and function of small interfering RNAs (siRNAs), microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs). In addition, we briefly review the relevance of small and long non-coding RNAs to human physiology and pathology and their potential to be exploited as therapeutic agents.Critical Reviews in Biochemistry and Molecular Biology 10/2013; 49(1). DOI:10.3109/10409238.2013.844092 · 5.81 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Advances in nanotechnology have provided powerful and efficient tools in the development of cancer diagnosis and therapy. There are numerous nanocarriers that are currently approved for clinical use in cancer therapy. In recent years, biodegradable polymer nanoparticles have attracted a considerable attention for their ability to function as a possible carrier for target-specific delivery of various drugs, genes, proteins, peptides, vaccines, and other biomolecules in humans without much toxicity. This review will specifically focus on the recent advances in polymer-based nanocarriers for various drugs and small silencing RNA's loading and delivery to treat different types of cancer. WIREs Nanomed Nanobiotechnol 2013. doi: 10.1002/wnan.1242 For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors declare no conflicts of interest.Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 01/2014; 6(1):40-60. DOI:10.1002/wnan.1242 · 4.24 Impact Factor