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Book Review Antisense Drug Technology Edited by Stanley T. Crooke

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Surface and Thin Film Analysis
Edited by Henning
Bubert and Holger
Jenett. Wiley-VCH,
Weinheim 2002.
336 pp., hardcover
E 99.00.—ISBN
This book gives a broad overview of
including not only those in routine use
but some less common ones. The organization of the contents is rather unusual,
with the main part being divided according to the nature of the particles emitted
from a surface (electrons, ions, photons),
and an additional short chapter devoted
to scanning probe methods. In each
chapter the authors have set out to
explain the special capabilities and
fields of application of the individual
methods. For those methods that have
become well established for technological applications, examples of their use
in solving industrial problems are also
described. Therefore, the book is a
useful work of reference both for readers in an academic research environment and for those seeking solutions to
technological problems of surface characterization. The necessary mathematical background is adequately covered
and is well illustrated by diagrams and
graphics where appropriate. Each
method is treated at a level of detail
and depth that gives a good overview,
while the literature references allow the
reader to find more thorough discussions of the theoretical background if
needed. Most of the figures and graphics
are clearly understandable, although the
Angew. Chem. Int. Ed. 2003, 42, 1083 – 1084
quality of some of the photographic
reproductions leaves something to be
desired (e.g., Figs. 2.33, 3.15, 4.23). The
appendix contains tables in which the
different methods are compared, enabling one to get a quick impression of
their strengths and limitations in various
areas of application. A list of instrument
manufacturers and suppliers is provided
at the end of the book, so that the reader
can approach these to enquire about
suitable equipment for specific applications; however, it appears that for some
methods the market leader in the field is
not listed.
A significant criticism of the book in
my view is that it is excessively biased
towards the analysis of inorganic materials. In recent years there has been a
growing trend towards the use of organically modified surfaces in microfabrication and sensor technology, and such
systems are likely to generate many
analytical problems that need to be
addressed. Unfortunately, for nearly all
the methods covered in the book, the
“thin film analysis” mentioned in the
title has not been extended to include
Langmuir, Langmuir – Blodgett, and
self-assembling films. The neglect of
those aspects probably also explains
why the powerful synchrotron radiation
techniques for determining surface
structure, such as NEXAFS and GIXRD, only appear in the book in an
“also-ran” role. Moreover, some simple
and widely used methods, such as measurements of contact angles or zeta
potentials, are missing from the book.
Also, for readers concerned with
organic and biological applications, it
would have been useful to include
chapters on surface plasmon resonance,
Brewster angle microscopy, and waveguide reflectance spectroscopy.
In addition to the lack of balance
between different areas of application,
another shortcoming is that scanning
methods are not given enough attention.
It is true that in their introduction the
authors explain that they have deliberately avoided discussing such imaging
methods in detail, but nevertheless they
should have given a much clearer
description of the scanning-tunneling
probe method as a spectroscopic tool
for elemental and density of states
analysis, including recent advances in
that field.
< 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
To summarize, the book is a useful
reference source that provides a good
overview of methods, enabling the
reader to choose the best approach to
solving a specific analytical problem. It
will also give stimulating ideas for every
researcher whose work is concerned
with surfaces and/or thin films.
Andreas Terfort, Markus Brunnbauer
Institut f,r Anorganische Chemie
Universit/t Hamburg (Germany)
Antisense Drug Technology
Edited by Stanley T.
Crooke. Marcel
Dekker, New York
2001. 929 pp.,
$ 225.00.—ISBN
With the knowledge of the human
genome sequence, the development of
gene-specific technologies is becoming
of considerable interest for both functional genomics and therapeutics,
including oligonucleotide-based strategies. Antisense Drug Technology provides a general overview of oligonucleotide-based applications, covering the
advantages, current obstacles, and
future directions. The difficulties that
will need to be overcome to make
oligonucleotides useful therapeutics are
highlighted in this book, such as problems concerning chemical stability,
delivery, mechanisms of action, and
target accessibility. These various
aspects are, in many respects, similar
for all types of oligodeoxynucleotides,
including the novel and highly promising “interfering oligoribonucleotides”
that have emerged since the publication
of this book.
The book begins with an introductory Part I (5 chapters) giving a good
overview of the potential and limitations
of the field. This section includes basic
principles of antisense technology and
the chemical, biochemical, and biophys-
0044-8249/03/4210-1083 $ 20.00+.50/0
ical requirements for obtaining oligonucleotide-based drugs. An example of an
application in signal transduction is
described to illustrate their use as a
tool for further understanding molecular processes as well as a novel class of
gene-specific therapeutic agents.
Part II (6 chapters) describes the
properties of the first generation of
antisense oligonucleotides, the phosphorothiates. These chapters summarize
what is known concerning their chemistry, pharmacokinetics, toxicology, and
therapeutic promises. The chapter ends
with a recapitulative focus on their
biological activities, both those expected
and those that are undesirable.
Part III (22 chapters) deals with the
recent development of novel classes of
oligonucleotides that have been
designed to overcome weaknesses
observed with the phosphorothioates.
This section starts by describing novel
promising chemistries such as locked
nucleic acids, peptide nucleic acids,
morpholino- and 2’-O-(2-methoxy)ethyl-modified oligonucleotides, and
also oligonucleotide conjugates. Such
new oligonucleotides provide increased
potency, increased nuclease resistance,
longer sustained action, and reduced
toxicity (5 chapters).
Next, a variety of successful applications of antisense oligonucleotides are
described. Activities of oligonucleotides
in immune stimulation and in modification of the splicing patterns of genes are
described, in addition to their conventional use in down-regulating gene
expression. Indeed, antisense oligonucleotides have been mainly used as
gene-specific inhibitors, and especially
as isotype-specific inhibitors, thereby
allowing the investigation and clarification of complex pathways. Some of these
inhibitors are presently under evaluation for therapeutic applications, in
treating inflammatory diseases, in transplantation medicine, and in treating
cancer and viral infections. Two types
of approaches are being pursued: antisense oligonucleotides can be administered either alone as a single-agent
therapy if a disease-specific gene is
identified, or in combination with existing therapeutic agents with the goal of
develping less toxic treatments. Finally,
this section describes how the development of novel formulations and delivery
routes is facilitating the treatment of a
wider variety of target tissues and cells
with oligonucleotides through increased
efficiency and stability. Such improvements will include not only parenteral
delivery of simple aqueous solutions but
also topical, pulmonary, and oral delivery.
approaches that make use of ribozymes
and antigene molecules are also discussed (3 chapters). The latter are codereading molecules that target DNA and
have been reported to interfere successfully with DNA metabolism. They offer
new opportunities for controlling DNAassociated functions and for directing
DNA-targeted antitumor agents to specific sequences. These advances could
markedly increase their selectivity and
minimize their toxic effects.
Each subject is covered in sufficient
detail to provide a good overview, and a
comprehensive list of references is
included for each chapter so that more
detailed descriptions can be found if
required. The majority of topics are
critically reviewed and most chapters
truly cover their subject in depth. The
book is structured according to areas of
application as set out clearly in the table
of contents, and that has resulted in a
good overview with only limited repetitions between the chapters. Each chapter can be read easily on its own.
< 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/03/4210-1084 $ 20.00+.50/0
Chemists as well as biologists will find
it suitable because of an appropriate
balance between the two disciplines.
The book offers a good way of quickly
gaining a sound appreciation of the
many different aspects of oligonucleotide-based strategies for readers who are
not familiar with the field. Specialist
readers will find it a relevant and up-todate source of information, containing
stimulating questions for future developments.
New generations of antisense oligonucleotides with increased stability and
potency compared to first-generation
phosphorothioates have been described.
Very recently, interfering oligoribonucleotides have been discovered. Both of
these oligonucleotide-based approaches
are used for down-regulation of a
selected gene by selective RNA degradation. Antisense oligonucleotides are
unique in that they can maintain RNA
integrity, thanks to strategies based on
RNase-H-resistant chemistry. Such
chemically modified antisense oligonucleotides can thus be used to induce
controlled enhancement of function by
interfering with splicing, and to inhibit
ribonucleoprotein activities such as telomerase action. In any case these technologies will benefit in the future from
an enhanced knowledge of transfection
conditions and in vivo disposition of
oligonucleotides. Such improvements
will soon enable oligonucleotides to
fulfill their promise in functional
genomics, in drug-target validation,
and in human therapeutics. Finally, I
strongly recommend this book for
everyone concerned with gene-specific
technologies in medicinal chemistry.
Carine Giovannangeli
Muséum National d’Histoire Naturelle
Laboratoire de Biophysique
Paris (France)
Angew. Chem. Int. Ed. 2003, 42, No. 10
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drug, stanley, antisense, book, technology, edited, crooked, review
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