The triumphant success of RNA interference (RNAi) in life sciences
is based on its high potency to silence genes in a
sequence-specific manner. Nevertheless, the first task for
successful RNAi approaches is the identification of highly active
small interfering RNAs (siRNAs). Early on, it has been found that
the potency of siRNAs can vary
drastically. Great progress was made when thermodynamic properties 
that influence siRNA activity were discovered. Design
algorithms based on these parameters enhance the chance to
generate potent siRNAs. Still, many siRNAs designed accordingly
fail to silence their targeted gene, whereas others are highly
efficient despite the fact that they do not fulfil the recommended
criteria. Therefore, the accessibility of the siRNA-binding site
on the target RNA has been investigated as an additional parameter
which is important for RNAi-mediated silencing. These and other
factors which are crucial for successful RNAi approaches will be
discussed in the present review.

Jens Kurreck

siRNA Efficiency: Structure or Sequence—That Is the Question

Several signalling proteins involved in cell growth and differentiation represent attractive candidate targets for cancer diagnosis and/or therapy since they can act as oncogenes. Because of their high specificity and low immunogeneicity, using artificial small noncoding RNA (ncRNAs) as therapeutics has recently become a highly promising and rapidly expanding field of interest. Indeed, ncRNAs may either interfere with RNA transcription, stability, translation or directly hamper the function of the targets by binding to their surface. The recent finding that the expression of several genes is under the control of small single-stranded regulatory RNAs, including miRNAs, makes these genes as appropriate targets for ncRNA gene silencing. Furthermore, another class of small ncRNA, aptamers, act as high-affinity ligands and potential antagonists of disease-associated proteins. We will review here the recent and innovative methods that have been developed and the possible applications of ncRNAs as inhibitors or tracers in cancer medicine.

Laura Cerchia

Vittorio De Franciscis

Noncoding RNAs in Cancer Medicine

The completion of the genome sequencing for several organisms has created a great demand for genomic tools that can systematically analyze the growing wealth of data. In contrast to the classical reverse genetics approach of creating specific knockout cell lines or animals that is time-consuming and expensive, RNA-mediated interference (RNAi) has emerged as a fast, simple, and cost-effective technique for gene knockdown in large scale. Since its discovery as a gene silencing response to double-stranded RNA (dsRNA) with homology to endogenous genes in Caenorhabditis elegans (C elegans), RNAi technology has been adapted to various high-throughput screens (HTS) for genome-wide loss-of-function (LOF) analysis. Biochemical insights into the endogenous mechanism of RNAi have led to advances in RNAi methodology including RNAi molecule synthesis, delivery, and sequence design. In this article, we will briefly review these various RNAi library designs and discuss the benefits and drawbacks of each library strategy.

Julie  Clark

Sheng  Ding

Generation of RNA<small.letters>i</small.letters> Libraries for High-Throughput Screens

In the past few years, the discovery of RNA-mediated gene
silencing mechanisms, like RNA interference (RNAi), has
revolutionized our understanding of eukaryotic gene expression.
These mechanisms are activated by double-stranded RNA (dsRNA) and
mediate gene silencing either by inducing the sequence-specific
degradation of complementary mRNA or by inhibiting mRNA
translation. RNAi now provides a powerful experimental tool to
elucidate gene function in vitro and in vivo, thereby opening new
exciting perspectives in the fields of molecular analysis and
eventually therapy of several diseases such as infections and
cancer. In hematology, numerous studies have described the
successful application of RNAi to better define the role of
oncogenic fusion proteins in leukemogenesis and to explore
therapeutic approaches in hematological malignancies. In this
review, we highlight recent advances and caveats relating to the
application of this powerful new methodology to hematopoiesis.

Letizia Venturini

Matthias Eder

Michaela Scherr

RNA-Mediated Gene Silencing in Hematopoietic Cells

C5a, one of the most potent inflammatory peptides, induces its
inflammatory functions by interacting with C5a receptor (C5aR)
that belongs to the rhodopsin family of seven-transmembrane G
protein-coupled receptors. C5a/C5aR signaling has been implicated
in the pathogenesis of many inflammatory and immunological
diseases such as sepsis and acute lung injury. Widespread
upregulation of C5aR has been seen at both the protein level and
transcriptional level under pathological conditions. Here, we show
that C5aR gene expression can be specifically suppressed by siRNA,
both in vitro and in vivo. A panel of chemically siRNA
oligonucleotides was first synthesized to identify the functional
siRNA sequences. The short hairpin RNAs (shRNAs) were also
designed, cloned, and tested for the silencing effects in C5aR
transfected cells. The effective shRNA expression cassettes were
then transferred to an adenovirus DNA vector. ShRNA-expressing
adenoviruses were intratracheally administered into mouse lung,
and a significant in vivo silencing of C5aR was obtained four days
after administration. Thus, C5aR shRNA-expressing adenoviruses
appear to be an alternative strategy for the treatment of
complement-induced disorders.

Lei Sun

Hongwei Gao

Vidya J. Sarma

Ren-feng Guo

Peter A. Ward

Adenovirus-Mediated In Vivo Silencing of Anaphylatoxin Receptor C5aR

RNA interference (RNAi) is a powerful method for specific gene
silencing which may also lead to promising novel therapeutic
strategies. It is mediated through small interfering RNAs (siRNAs)
which sequence-specifically trigger the cleavage and subsequent
degradation of their target mRNA. One critical factor is the
ability to deliver intact siRNAs into target cells/organs in vivo.
This review highlights the mechanism of RNAi and the guidelines
for the design of optimal siRNAs. It gives an overview of studies
based on the systemic or local application of naked siRNAs or the
use of various nonviral siRNA delivery systems. One promising
avenue is the the complexation of siRNAs with the polyethylenimine
(PEI), which efficiently stabilizes siRNAs and, upon systemic
administration, leads to the delivery of the intact siRNAs into
different organs. The antitumorigenic effects of
PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant
proteins like in mouse tumor
xenograft models are described.

Achim Aigner

Delivery Systems for the Direct Application of siRNAs to Induce
       RNA Interference (RNAi) In Vivo

About this journal

BioMed Research International publishes original research articles and&nbsp;review articles covering a wide range of subjects within the biomedical sciences. The journal will accept both basic and translational research.

Journal profile

Meet the editorial board

BioMed Research International maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Special Issues

Author guidelines

Editorial board

Databases and indexing

title

BioMed Research International publishes original research articles and review articles covering a wide range of subjects within the biomedical sciences. The journal will accept both basic and translational research.

description

https://images.hindawi.com/journals/bmri/bmri.banner.jpg

twitter:card

twitter:description

twitter:site

twitter:title

twitter:url

twitter:image

BioMed Research International | Hindawi

BioMed Research International

This Issue is now open for submissions.
Papers are published upon acceptance, regardless of the Special Issue publication date.

BioMed Research International

RNA Interference

RNA Interference

Articles

siRNA Efficiency: Structure or Sequence—That Is the Question

Noncoding RNAs in Cancer Medicine

Generation of RNAi Libraries for High-Throughput Screens

RNA-Mediated Gene Silencing in Hematopoietic Cells

Adenovirus-Mediated In Vivo Silencing of Anaphylatoxin Receptor C5aR

Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo