Biomedical Engineering Reference
In-Depth Information
CHAPTER 7
Polymeric Micelle-Based
Nanomedicine for siRNA
Delivery
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XI-QIU LIU, XIAN-ZHU YANG AND JUN WANG*
CAS Key Laboratory of Brain Function and Disease, and School of Life
Sciences, University of Science and Technology of China, Hefei, Anhui
230027, P. R. China
*
E-mail: jwang699@ustc.edu.cn
7.1 Introduction
The RNA interference (RNAi) machinery was first discovered in plants; this
post-transcriptional gene-silencing mechanism was subsequently demonstrated
by Fire and Mello in Caenorhabditis elegans.
1,2
Two approaches utilize RNAi
to inhibit target genes: short hairpin RNA (shRNA) and small interfering
RNA (siRNA).
3
Sequence-specific 21-23 base-pair double-stranded siRNA
selectively degrades complementary messenger RNAs (mRNAs).
4,5
Inside the
cell, siRNA is incorporated into the RNA-induced silencing complex (RISC),
which separates the strands of the RNA duplex and discards the sense strand.
The antisense RNA strand then guides the activated RISC to anneal and
cleave the target mRNA.
6
An endonuclease, Argonaute 2, plays a key role in
unwinding the duplex (sense and antisense siRNA strands) and degrading the
target mRNA.
7
siRNA molecules can block specific expression of endogenous
and heterologous genes in various mammalian cell lines.
5
In addition to
biological research and drug development, siRNA has tremendous therapeutic
