:
Before writing their manuscripts, potential authors of
review articles
should forward the title and a short abstract to the Guest Editor. The
Guest Editor will then provide feedback on the suitability of the topic
upon
consultation with other editors and/or members of the Editorial Board.
Authors
are encouraged to write reviews that provide a critical appraisal of
areas of Nucleic Acid Derivatives in Emerging Technologies.
Department
of Mathematics, Visva-Bharati, Santiniketan 731235, West Bengal, India;
E-mail: itsmedip@rediffmail.com; dmazumda@science.uva.nl
Department
of Medicinal Chemistry & Natural Products, School of Pharmacy -
Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Tel:
972-50-6272355; e-mail: avid@ekmd.huji.ac.il
Recent
Updates in DNA Incorporated Carbon Nanotubes and Metal Nanoparticles
for Electrochemical Sensors and Biosensors - A Review
Department
of Chemical Engineering and Biotechnology, National Taipei University
of Technology, No.1, Section 3, Chung-Hsiao East Road , Taipei 106,
Taiwan (ROC); E-mail: smchen78@ms15.hinet.net
DNA, carbon nanotubes, metal nanoparticles,
electrochemical sensors and biosensors.
Howard
Hughes Scholar, Institute of Enzymology, Hungarian Academy of Sciences,
Karolina 29, H-1113, Budapest, Hungary; E-mail: vertessy@enzim.hu
Abstract:
There
are two ways that may lead to appearance of uracil in DNA under
physiological circumstances. First, frequent and spontaneous
deamination of cytosine leads to formation of uracil with a
frequency of around several hundred evenyts/day in mammalian genomes.
This alteration changes the base-pairing character and will lead to a
point mutation (replacement of a C:G base pair with an A:U base pair)
in the next replication cycle. Second, uracil may get incorporated to
replace thymine if the cellular ratio of the respective building blocks
dUTP/dTTP is elevated. Thymine-replacing uracils are not mutagenic per
se but may lead to recognition perturbances. Repair of uracil-DNA is
initiated by uracil-DNA glycosylases. In addition to the mistake
character of uracil in DNA, recent data indicate that this base may
have specific signal transduction role as well in diversification of
immunoglobulin genes and in initiating cell death during metamorphosis.
Specific recognition of uracil-DNA has found applications in genetic
engineering and also in cancerchemotherapy. The present review covers
recent developments and provides an outlook in this field.
Manuscript ID: IJMS-20-14
Type: Review
Title:Peptide-based strategy
for ex-vivo and in vivo delivery of nucleic acids and derivatives
Authors: L. Crombez and Gilles Divita
Affiliations:
CRBM - CNRS -FRE-2593, Molecular Biophysics & Therapeutics, 1919
route de Mende, 34293 Montpellier cedex 5, FRANCE; Tel: + 33 (0)4 67 61
33 92; Fax: 33 (0)4 67 52 15 59; E-mail : gilles.divita@crbm.cnrs.fr
Abstract:
The major obstacle to clinical development of most of the nucleic
acid-based strategies, including short interfering RNAs, is their poor
cellular uptake and bioavailability. Although, several viral and
non-viral strategies have been proposed to improve nucleic acids
delivery their applications in vivo remain a major challenge. Several
new technologies have been designed to improve cellular uptake of
therapeutic molecules, including cell-penetrating peptides (CPPs),
which represent a new and innovative concept to bypass the problem of
bioavailability of drugs. Two CPP-strategies have been described so
far, the first one requires chemical linkage between the drug and the
carrier for cellular drug internalization and the second is based on
the formation of stable complexes with drugs depending on their
chemical nature. We have developed a new strategy, based on a short
amphipathic peptides, MPG/PEP, that are able to form stable
nanoparticles with nucleic acids and can efficiently deliver siRNA in a
fully biologically active form into a variety of cell lines and in
vivo. This short review will discuss the mechanism and the potency of
the non-covalent peptide-based strategy for nucleic acid and derivative
delivery both in vitro and in vivo.
Manuscript ID: IJMS-20-15
Type: Review
Title: Nucleic Acid Derived
Indices in Marine Ecology
Authors: Maria Alexandra Chícharo
Affiliations: CCMAR/University
of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; E-mail:
mchichar@ualg.pt; URL: http://w3.ualg.pt/~mchichar/
Abstract: Some of most used
indices in marine ecology are nucleic acids derived indices. They can
be divided in three target levels: 1) at organism level indices, such
as RNA/DNA ratios, DNA/dry weight RNA/protein, 2) at population
level as starvation incidence, and 3) community level such as exergy
indices. The nucleic acids derived indices have been applied with
success as indicators of nutritional condition, well been and growth in
aquatic invertebrates and fishes. They are also useful as stress
indicators of anthropogenic impacts in marine population and
communities, such as dredge fisheries or eutrophication. The paper will
also include a general characterization of most used nucleic acid
derived indices in marine ecology, a description of the methodology and
also advantages and limitations of them.
Manuscript ID: IJMS-20-16
Type: Review
Title: Nucleic Acid Derived
Indices in Marine Ecology
Authors: N. F. Azevedo
1,2,
C. Almeida
1,2, C. W. Keevil
2 and M. J.
Vieira
1,*
Affiliations: 1 1IBB -
Institute for Biotechnology and Bioengineering, Centre for Biological
Engineering, Universidade do Minho, Campus de Gualtar 4710-057, Braga,
Portugal 2 2Environmental Healthcare Unit, School of Biological
Sciences, University of Southampton, Bassett Crescent East, Southampton
SO16 7PX, United Kingdom; * Author to whom correspondence should be
addressed; E-Mail:
mjv@deb.uminho.pt
Abstract: Fluorescence in situ
hybridization (FISH) is a well-established technique that is used for a
variety of purposes, ranging from pathogen detection in clinical
diagnostics to the determination of chromosomal stability in stem cell
research. The key step of FISH involves the detection of a nucleic acid
region and as such, DNA molecules have typically been used to probe for
the sequences of interest. However, since the turn of the century, an
increasing number of laboratories have started to move on to the more
robust DNA mimics methods, most notably peptide and locked nucleic
acids (PNA and LNA). In this review, we will cover the state-of-the-art
of the different DNA mimics in regard to their application as efficient
markers for the presence of individual microbial cells, and consider
their potential advantages and pitfalls. Available probes are then
assessed in terms of theoretical sensitivity and specificity. In
addition, a list of what remains to be done to further impose this
method as a gold-standard for the whole-cell detection of
microorganisms in different settings is presented.
Manuscript ID: IJMS-20-17
Type: Review
Title: Key RNA labeling
technologies to tackle sizeable problems in structural biology
Authors: Kwaku T. Dayie
Affiliations:
Lerner Research Institute, Department of Molecular Genetics and Center
for Structural Biology, Cleveland Clinic, 9500 Euclid Avenue,
Cleveland, OH, 44195
Abstract:
The ability to adopt complex three-dimensional (3D) structures that can
rapidly interconvert between multiple functional states (folding and
dynamics) is key for the proper functioning of RNAs. Consequently, it
has become axiomatic that RNA structure and dynamics necessarily
determine their biological function. In the post-genomic era, it is
clear that RNAs comprise a larger proportion (>50%) of the
transcribed genome compared to proteins ( 2%). Yet the determination
of the 3D structures of RNAs lags considerably behind those of proteins
and to date there are even fewer investigations of dynamics in RNAs
compared to proteins. Site-specific incorporation of various structural
and dynamic probes into nucleic acids (NA) promises to revolutionarize
NA structural biology in this postgenomic era. We, therefore,
critically assess here various methods for introducing probes into NA
for structural, functional, and biotechnological applications. The
probes surveyed include non-radioactive stable isotopes (2H, 13C, 15N,
19F, 77Se) and photo-stable fluorophores. Incorporation of these probes
using improved RNA ligation strategies promise to change the landscape
of structural biology of supramacromolecules probed by biophysical
tools such as NMR spectroscopy, X-ray crystallography, Fluorescence and
Raman spectroscopy. Finally, we outline some of the structural and
dynamic problems that could be amenable to these technological advances.
Keywords:
dynamics, FRET, isotopic labeling, ligation, Mass Spectrometry, NMR,
Raman, RNA dynamics and folding and structure, X-ray crystallography.
Manuscript ID: IJMS-20-19
Type: Full Research Paper
Title:
Designs and efficacies of broad-spectrum and virus-specific approaches
using nucleic acid-based agents against influenza A viruses
Authors: Jonathan Wong
Affiliations:
Molecular Biology Group, Biotechnology Section, Defence R&D Canada
– Suffield, Box 4000 Main Station, Medicine Hat, Alberta, Canada
T1A 8K6
Abstract: The global
increases in the number of influenza A virus isolates resistant to
amantadine and tamiflu undermine our ability to defend against
potential influenza pandemics. There are compelling reasons to
fast track research and development of novel antiviral agents which can
protect against drug-resistant and potentially pandemic strains of
deadly influenza viruses. Nucleic acid-based drugs
represent a promising class of antiviral agents that could play a role
in the prevention and treatment of influenza virus infections.
Antisense oligonucleotides designed to inhibit the expressions of key
virus proteins (nucleoprotein, heamagglutinin and polymerase) have been
designed and are found to be therapeutically effective against
influenza A viruses in both tissue culture and animal studies.
Gene-silencing approaches such as antisense and small interfering RNA
are highly sequence specific and their efficacies can be compromised by
antigenic shifts and drifts in virus genes. Alternatively, nucleic
acids such as ds RNA and oligonucleotides containing unmethylated CpG
motifs can be designed to elicit antiviral immunity via the toll-like
receptor (TLR-3 and -9, respectively) activation pathways.
Efficacy studies in mice have shown that ds RNA such as poly ICLC can
provide effective and broad-spectrum protection against lethal
challenges against various strains of influenza A virus, including
seasonal and avian H5N1. Similarly, CpG-containing
oligonucleotides (15-22-mers) have been shown to be effectively against
influenza A viruses. The versatility and potency of nucleic
acid-based drugs make them potential drug candidates which could be
used in conjunction with existing antiviral drugs to combat seasonal or
pandemic influenza virus infections.
Type: Review
Title: Recent developments in
peptide-based cellular delivery of nucleic acids
Authors: Sandra Veldhoen,
Sandra D. Laufer and Tobias Restle
Affiliations:
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Institute of
Molecular Medicine, Ratzeburger Allee 160, 23538 Lübeck, Germany
Abstract:
Cell penetrating peptides (CPPs) represent a rapidly expanding family
of peptides capable of translocating large hydrophilic cargos (e.g.
nucleic acids) across cell membranes. Based on various studies it has
been concluded that translocation results from direct, physical
transfer through the lipid bilayer of the cell membrane. Yet, the
majority of those studies relied upon fluorescence imaging and flow
cytometry analysis of chemically fixed cells to examine intracellular
delivery. The cell fixation procedures applied in the course of these
experiments led to localization artefacts of cargo and carrier inside
the cell and misinterpretation of the data. More recent studies provide
convincing evidence for the involvement of endocytosis as the
dominating mechanism for cellular internalization. Consequently, our
knowledge about CPPs and their mechanism of action has to be revised.
Thus, even well studied peptides like Tat or penetratin are currently
re-investigated. Nowadays it is generally accepted in the field that
microscopic studies have to be performed with non-fixed cells and that
extracellularly bound CPPs, an additional source of artefacts, have to
be removed carefully. The re-evaluation of several CPPs in the presence
or absence of cargo yielded compelling evidence that the uptake is
initially mediated by interactions with components of the extracellular
matrix responsible for the attachment of the complexes. Additionally,
most recent publications suggest the possibility of multiple pathways
involved in cellular entry. Furthermore, much emphasis is given to the
fact that the chemical cross-linking of a CPP with a cargo as well as
non-covalent complexation may considerably alter its properties and
accordingly the mechanism of uptake. In this review, we will summarize
the latest developments in peptide-based cellular delivery of nucleic
acid cargos. We will discuss different mechanisms of entry, the
intracellular fate of the cargo, correlation studies of uptake versus
biological activity of the cargo as well as technical problems and
pitfalls.
Type: Review
Title: MicroRNA: A Potential Therapeutic Target and
Intervention Tool
Authors: Zhen Liu, Alhousseynou Sall and Decheng Yang
Affiliations: Department
of Pathology and Laboratory Medicine, The James Hogg iCapture Center,
University of British Columbia, Vancouver, Canada
Abstract: MicroRNAs
(miRNAs) are a class of 20 to 24-nt non-coding RNAs that
post-transcriptionally regulate target mRNA by imperfect base-pairing
with the 3’-untranslated region (3UTR) or other targets to inhibit
translation or RNA stability. To date, more than 460 human miRNAs have
been experimentally identified, and estimated to regulate more than one
third of cellular messenger RNAs.
Besides their essential
physiological role in mammalian development and tissue identity, their
significance in human disease is just beginning to be disclosed.
Accumulating evidence has linked the deregulated expression patterns of
miRNAs to a variety of diseases, such as cancer, cardiovascular
diseases and viral infections. Studies in human cancer indicate
different individual miRNAs can act as either classical tumor
suppressor or oncogenes, revealing the potential of phenotype recovery
through miRNA intervention. Differentially regulation of cardiac
specific miRNAs, e.g. the primarily miR-1 and miR-133, has also shown
to be correlated with cardiac hypertrophy and other heart diseases.
Some viruses not only encode their own miRNA targeting viral and
cellular genes for regulating latency and avoiding host immune
response, but also may take the advantage to exploit cellular miRNA
machinery for its own replication, thereby possibly contributing to
their tissue tropism, one of the striking example is the liver enriched
miR-22 bind to 5’UTR of HCV and promotes its replication.
miRNAs
provide its particular layer of network for gene regulation, thus
possessing the great potential both as a novel class of therapeutic
targets, and as a powerful intervention tool, adding to the routinely
used nucleic acid-based gene-silencing molecules such as siRNAs.
In this regard, different types of modified antisense oligonucleotides,
including 2’-OMe, 2’-MOE and LNA that are complementary to mRNA
targets, have shown certain success of inhibiting specific endogenous
miRNAs both in vitro and in vivo. Alternatively, synthetic mRNAs that
contain the binding sites of miRNA can work as “decoy” or “miRNA
sponge” to inhibit the function of specific miRNA. On the other hand,
to overexpress specific miRNAs, various miRNA expression vectors and
double-stranded miRNA mimetics have been experimentally validated.
miRNA expression vectors with a pol II promoter have shown the promise
of tissue-specific and inducible expression. Endogenous precursor
miRNAs have also been used as scaffolds for the expression of RNA
interference, which exhibited the advantage on specificity and efficacy
over common short hairpin RNA. Artificial miRNAs can also be designed
for specific target sets or with modulated specificity. In this article
we will review the recent progress on this emerging technology as a
powerful tool for gene regulation studies and as a rationale strategy
for development of therapeutics. In addition, the limitations and
challenges on the potential application of these miR-based
interventions will also be discussed.
Type: Review
Title: Enhanced allelic discrimination ability of
a Locked Nucleic Acid attached at the 3'-end of oligonucleotide
Authors: Yuichi
Michikawa, Tomo Suga, Yoshimi Ohtsuka, Mayumi Iwakawa, Takashi Imai
Affiliation: RadGenomics
Project, Research Center for Charged Particle Therapy National
Institute of Radiological Sciences, Japan
E-mail: y_michi@nirs.go.jp