RNA interference and its therapeutic potential

Central European Journal of Medicine (Impact Factor: 0.15). 04/2011; 6(2):137-147. DOI: 10.2478/s11536-011-0005-5


RNA interference is a technique that has become popular in the past few years. This is a biological method to detect the activity
of a specific gene within a cell. RNAi is the introduction of homologous double stranded RNA to specifically target a gene’s
product resulting in null or hypomorphic phenotypes. This technique involves the degradation of specific mRNA by using small
interfering RNA. Both microRNA (miRNA) and small interfering RNA (siRNA) are directly related to RNA interference. RNAi mechanism
is being explored as a new technique for suppressing gene expression. It is an important issue in the treatment of various
diseases. This review considers different aspects of RNAi technique including its history of discovery, molecular mechanism,
gene expression study, advantages of this technique against previously used techniques, barrier associated with this technique,
and its therapeutic application.

KeywordsCancer–MicroRNA–Interfering RNA–Disease

  • [Show abstract] [Hide abstract]
    ABSTRACT: It is important to obtain structure-activity relationship (SAR) data across cationic lipids for the self-assembly and nonviral intracellular delivery of siRNA. The aims of this work are to carry out a SAR study on the efficiency of asymmetrical N(4),N(9)-diacyl spermines in siRNA delivery and EGFP reporter gene silencing, with comparisons to selected mixtures composed of symmetrical N(4),N(9)-diacyl spermines. Another important aim of these studies is to quantify the changes in cell viability, assayed with alamarBlue, as a function of lipid structure. Therefore, we have designed, synthesized, purified, and assayed novel cationic lipids that are asymmetrical lipopolyamines based on spermine. Flow cytometry and fluorescence microscopy in an EGFP stably transfected HeLa cell line, measuring both delivery of fluorescently tagged siRNAs and silencing the EGFP signal, allowed quantitation of the differences between asymmetrical cationic lipids, mixtures of their symmetrical counterparts, and comparison with commercial nonviral delivery agents. Intracellular delivery of siRNA and gene silencing by siRNA differ with different hydrophobic domains. In these asymmetrical N(4),N(9)-diacyl spermines, lipids that enhance siRNA uptake do not necessarily enhance siRNA-induced inhibition of gene expression: C18 and longer saturated chains promote uptake, while more unsaturated C18 chains promote gene silencing. These properties are efficiently demonstrated in a new nontoxic cationic lipid siRNA vector, N(4)-linoleoyl-N(9)-oleoyl-1,12-diamino-4,9-diazadodecane (LinOS), which is also shown to be comparable with or superior to TransIT-TKO and Lipofectamine 2000.
    Molecular Pharmaceutics 11/2011; 9(7). DOI:10.1021/mp200429n · 4.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Head and neck squamous cell cancer (HNSCC) is the six most common cancer in the world. In attempts to improve therapy of this cancer, contemporary research is focused predominantly on new tumor markers and evaluation of their diagnostic, prognostic and predictive significance for routine clinical practice. Molecular tumor markers at the same time very well reflect pathobiological processes in tumors. New etiological and pathobiological aspects of cancerogenesis of HNSCC were lately introduced. Namely epigenetic mechanisms, RNA interference and microRNA, cancer stem cells and epithelial-mesenchymal transition play important role in cancerogenesis as well as represent new source of molecular tumor markers and potential target of biological therapy.
    Onkologie 10/2012; 6(5):241-246. · 0.86 Impact Factor