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本帖最后由 细胞海洋 于 2011-6-25 11:08 编辑
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6 I8 u4 Z: M$ yPreface6 U/ g, H7 }' v3 x4 V
Little over a decade ago, Andrew Fire, Craig Mello, and colleagues demonstrated that : L( e N6 c2 |! f
double-stranded (ds)RNA induces sequence-specifc gene silencing in the nematode ; Y# S4 a. O6 _1 y k$ w
Caenorhabditis elegans (RNA interference, RNAi). This work converged with research in 2 K* E* L& t( C8 S! n" S, E
plants, in which related RNA-based silencing processes were known to exist. Ever since, ! i4 k4 _) G. l5 Y( n6 C0 j! T+ |( e" L" X
research in the feld has progressed at an astonishing rate, resulting in our appreciation of
/ f0 c5 G( a" M* s/ c7 F9 Bsmall silencing RNAs as central regulators of gene expression, as guards of genome integ-% l5 O! {# D1 V
rity, and as essential mediators of antiviral defense. The discovery that synthetic small # f% r2 {1 g- f/ f9 m( T0 Q2 T
interfering RNA (siRNA) induces gene silencing in mammals, by Thomas Tuschl and col-
5 f# b; g6 B1 ~6 v L; W* _2 A' Jleagues in 2001, has further boosted the development of novel therapeutics and experi-
2 {: @7 U% N6 dmental tools based on RNAi technology.; r0 S3 U, {8 Y
Viruses and RNAi share an intricate relationship at many levels. Early work in plants ) y! \$ Y# J5 |
indicated that viruses can be both inducers and targets of RNA-based post-transcriptional 5 P, `" _' C) i6 s" x( v
gene silencing (which we now know as RNAi or RNA silencing). The concept of RNAi as
+ ~4 S0 j- \5 E. man antiviral defense mechanism is now well-established in plants and other organisms,
`) |! ]! P L$ I5 dincluding insects. In vertebrates, viruses also interact with a related RNA silencing mecha-
7 s9 t1 I% x% L! K" m. e' v+ bnism, the microRNA (miRNA) pathway. Many nuclear DNA viruses encode their own set
* D) A# v, m0 X) k9 R' ~of miRNAs, by which they regulate viral or host gene expression and modify, for example,
/ Z' M7 E% E4 w2 B) Qthe transition from latent to lytic infection and the recognition of infected cells by the host
: }! H" d5 K4 i; rimmune system. Furthermore, cellular miRNAs likely regulate expression of many genes * P" o- m a% w( ^
that are important for virus biology, but they have been suggested to directly target viral 7 K# c# t; n( V3 f2 z
RNA as well.; y. s" j L0 N0 c6 o" ?' c6 D
The therapeutic potential of RNAi-based antiviral drugs was recognized early on. It is
% d. k5 z& t, P% P/ znow clear that replication of many, if not all, mammalian viruses can be suppressed by ( l) |3 i1 W5 [# o8 X# C, h
RNAi in cell culture. While these results have raised considerable optimism about the # x( J, I6 A' p0 \+ k3 b% F
potential of RNAi-based drugs, important hurdles remain, including issues related to the ! o' F. L1 q+ M3 T W/ L y1 b# X
delivery and stability of siRNAs and the risk of viral escape.7 q: T2 U3 w0 X" B( c
From this brief overview it will be apparent that a great — and increasing — number
8 X; \7 Y6 d5 q/ s: Uof tools and techniques are available for those interested in the interface of viruses and
, I% F+ U4 u, w( Z: @ XRNAi. Antiviral RNAi: concepts, methods, and applications provides a collection of proto-
* N# d3 g: S" w ~cols for the analysis of natural antiviral RNAi responses and viral miRNAs, as well as for
' }3 Y4 {# G. }. ^the development and optimization of RNAi-based antiviral drugs. As RNAi is a central {% P' z/ v# Y+ l9 S
regulatory mechanism in the cell, the methods in this volume can also be applied out of * x+ B) g5 W7 ?% K% d P& v
the context of a virus infection. In the established tradition of the Methods in Molecular
: u7 n5 r, H+ p$ ]* YBiology series, Antiviral RNAi: concepts, methods, and applications provides detailed step-
, p4 @$ T; z+ K4 O/ n0 Zby-step protocols and extra tools and tricks that should be useful to those new to the feld
+ p4 b. z. d$ ~2 J8 ^and experienced scientists alike.; X% ?# }' e; L
This volume consists of fve parts. Part 1 reviews important basic concepts in the feld
/ n7 C, A4 A. m5 a& ]+ mof antiviral RNAi. Part 2 provides experimental and bio-informatic tools for the analysis of $ W7 L2 `( J, H% S
small silencing RNAs. Part 3 covers methods to biochemically dissect RNAi-based antivi-' f" I) h }# O- P
ral defense and viral counter-defense mechanisms. Part 4 describes methods for the design, $ t0 W( N' l" I; M
expression, and delivery of therapeutic antiviral siRNAs. Part 5 presents genome-wide 5 E) m. U4 y% Q$ K0 Q, l2 @
RNAi approaches for the identifcation of factors involved in virus replication, which may
K9 h' K+ w3 g% W8 \represent novel targets for antiviral therapy.
( V* |; {, Q: w& S; R/ }+ ]% ?I am grateful to all authors for providing their outstanding contributions and to John
* ]1 n9 Z+ s- D) _# Q5 u7 E8 ]Walker for guidance while editing this volume. I thank members of my lab, especially # L' x7 c( Q* O8 I% P2 c2 v- H
Walter Bronkhorst, Koen van Cleef, Marius van den Beek, and Joël van Mierlo, for discus-0 T% B: Z4 c0 E7 C
sions. I am thankful to Raul Andino for having been a great mentor and for introducing
& R4 ^- Q% G* f7 A$ ]- Q0 _5 C- U$ M4 Wme to this exciting feld of research. Finally, I would like to apologize for doing little jus-
4 N2 K; r% y a+ H6 P) h, Z# Ptice to the seminal work in plants; space limitations forced me to focus this volume on the
9 {3 q1 @. Q, s2 g: D& k }6 nanimal system.9 x2 w/ s/ D3 S$ |7 C3 Q9 J
Nijmegen, The Netherlands Ronald P. van Rij |
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发表于 2011-6-25 10:44
发表于 2011-6-25 11:09
